Atezolizumab (Tecentriq®/Tecentriq Hybreza™): A Comprehensive Oncological Review

1. Introduction to Atezolizumab (Tecentriq®/Tecentriq Hybreza™)

Atezolizumab is a humanized monoclonal antibody that functions as an immune checkpoint inhibitor by targeting Programmed Death-Ligand 1 (PD-L1).[1] As an antineoplastic agent, Atezolizumab belongs to the therapeutic class of anti-PD-L1 monoclonal antibodies.[5] Its clinical significance lies in its ability to modulate the host immune response against tumor cells, representing a pivotal advancement in cancer therapy.[6] Developed by Genentech, a member of the Roche Group, Atezolizumab has become a cornerstone in the treatment of various malignancies.[6] The medication is available in an intravenous formulation (Tecentriq®) and a subcutaneous formulation (Tecentriq Hybreza™), the latter co-formulated with hyaluronidase to facilitate subcutaneous delivery.[8]

The development and expanding applications of Atezolizumab exemplify the transformative shift in oncology towards immunotherapy, which harnesses the body's immune system to combat cancer. This approach targets key immune escape pathways exploited by tumors. The approval of Atezolizumab across a diverse range of cancer types, often in settings where previous therapeutic options offered limited efficacy, signifies a paradigm shift in cancer treatment strategies. Its progression from use in later lines of therapy to first-line and adjuvant settings further underscores its integral role in contemporary oncological practice.[7] This report aims to provide a comprehensive review of Atezolizumab, encompassing its pharmacological characteristics, detailed regulatory history with both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), extensive clinical trial data supporting its efficacy and safety, and its current clinical applications.

2. Chemical, Pharmaceutical, and Manufacturing Characteristics

Atezolizumab, identified by the DrugBank ID DB11595 and CAS Number 1380723-44-3, is classified as a biotech therapeutic agent.[5] It is a humanized IgG1 kappa monoclonal antibody.[1] The chemical structure is described as immunoglobulin G1, anti-(human CD antigen CD274) (human monoclonal MPDL3280A heavy chain), disulfide with human monoclonal MPDL3280A kappa-chain, dimer, with a molecular formula of C6446​H9902​N1706​O1998​S42​ and a calculated molecular mass of approximately 145 kDa.[1] Commonly used synonyms include MPDL3280A, MPDL 328OA, RG7446, and RO5541267.[1]

Atezolizumab is marketed under the brand names Tecentriq® for intravenous (IV) administration and Tecentriq Hybreza™ for subcutaneous (SC) administration.[8]

• Tecentriq (IV): Supplied as a concentrate for solution for infusion, it is a clear, colorless to slightly yellowish liquid. Available strengths are 840 mg/14 mL and 1200 mg/20 mL, both at a concentration of 60 mg/mL.[5] The solution has a pH of 5.5 - 6.1 and an osmolality of 129 - 229 mOsm/kg.[16]
• Tecentriq Hybreza (SC): This formulation combines atezolizumab with hyaluronidase-tqjs, an endoglycosidase that facilitates SC delivery. It is supplied as a solution for injection in a strength of 1875 mg atezolizumab and 30,000 units hyaluronidase per 15 mL.[8] Similar to the IV formulation, it is a clear, colorless to slightly yellowish liquid with a pH of 5.5 - 6.1, but with a higher osmolality of 359 - 459 mOsm/kg.[16]

Atezolizumab is produced using recombinant DNA technology in Chinese Hamster Ovary (CHO) cells.[3] A critical aspect of its design is the engineering of its Fc region. This modification is specifically implemented to reduce Fc effector functions, namely Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC).[1] Such engineering is intended to prevent the antibody from inadvertently targeting and destroying PD-L1-expressing T-effector cells, an action that could potentially compromise its anti-tumor activity. This highlights a sophisticated approach in antibody design aimed at maximizing therapeutic efficacy while minimizing potential off-target effects mediated by the antibody's Fc region, reflecting a nuanced understanding of antibody-immune cell interactions beyond simple antigen binding. Functional grade preclinical antibodies are manufactured in an animal-free facility using in vitro cell culture techniques and are purified by a multi-step process to ensure low levels of endotoxins and other contaminants.[35] The manufacturer of Atezolizumab is Genentech, Inc., a member of the Roche Group.[6]

Table 1: Atezolizumab Product Details

Feature	Details	References
Generic Name	Atezolizumab	User Query, 10
Brand Names	Tecentriq®, Tecentriq Hybreza™	8
Manufacturer	Genentech, Inc. (Roche Group)	6
DrugBank ID	DB11595	User Query, 10
CAS Number	1380723-44-3	User Query, 5
Type	Biotech; Humanized IgG1 kappa monoclonal antibody	User Query, 1
Molecular Formula	C6446​H9902​N1706​O1998​S42​	5
Key Synonyms	MPDL3280A, RG7446, RO5541267	1
Formulations	Tecentriq (IV): 840 mg/14 mL & 1200 mg/20 mL (60 mg/mL) concentrate for infusion.	5
	Tecentriq Hybreza (SC): 1875 mg atezolizumab + 30,000 units hyaluronidase/15 mL solution for injection.	8
Manufacturing Process	Produced in CHO cells by recombinant DNA technology; Fc-engineered to reduce ADCC/CDC.	1

3. Mechanism of Action: Targeting the PD-L1/PD-1 Pathway

Atezolizumab exerts its antineoplastic effects by targeting Programmed Death-Ligand 1 (PD-L1), also known as CD274 or B7-H1.[1] PD-L1 is a transmembrane protein that can be expressed on the surface of tumor cells as well as various tumor-infiltrating immune cells, including T-cells, B-cells, dendritic cells, and macrophages.[2]

Atezolizumab binds specifically to PD-L1, thereby preventing its interaction with its cognate receptors, Programmed Death-1 (PD-1; PDCD1) and B7.1 (CD80).[1] The PD-1 receptor is primarily expressed on activated T-cells, B-cells, and myeloid cells, while B7.1 is expressed on antigen-presenting cells and activated T-cells. The engagement of PD-L1 with PD-1 or B7.1 transmits an inhibitory signal that dampens T-cell activation, proliferation, cytokine production, and cytotoxic activity.[2] This PD-L1/PD-1 pathway is a crucial immune checkpoint that normally functions to maintain self-tolerance and modulate the duration and amplitude of physiological immune responses. However, many cancer types co-opt this pathway to evade immune surveillance and destruction.

By blocking the interaction of PD-L1 with both PD-1 and B7.1, Atezolizumab effectively removes these inhibitory signals, thereby restoring or enhancing T-cell-mediated anti-tumor immunity.[1] This mechanism can lead to the reactivation of previously suppressed tumor-specific T-cells, promoting their migration into the tumor microenvironment, proliferation, and ultimately, the killing of cancer cells.[2] The ability of Atezolizumab to inhibit PD-L1 binding to both PD-1 and B7.1 represents a dual blockade. This dual action may contribute to a broader impact on the immune response, as blocking the PD-L1/B7.1 interaction, in particular, has been suggested to enhance T-cell priming and activation within the lymph nodes, complementing the reinvigoration of T-cells directly within the tumor microenvironment.[7]

Atezolizumab has been engineered with a modified Fc region to minimize effector functions such as ADCC and CDC.[1] This design is intended to prevent the depletion of PD-L1-expressing immune cells, particularly T-effector cells, which could otherwise compromise the therapeutic efficacy of the antibody. Furthermore, Atezolizumab's mechanism involves selective sparing of the interaction between PD-1 and its other ligand, PD-L2 (B7-DC, CD273).[3] Since PD-L2 expression is more restricted (primarily on APCs) and may play distinct roles in immune tolerance and effector T-cell responses, preserving this interaction might contribute to a more favorable safety profile by maintaining certain aspects of immune homeostasis in normal tissues and potentially minimizing autoimmune reactions.[3]

The expression of PD-L1 on tumor cells or tumor-infiltrating immune cells is often utilized as a biomarker to predict response to Atezolizumab and other PD-1/PD-L1 pathway inhibitors.[2] However, the predictive value of PD-L1 expression is complex and not absolute. Clinical responses have been observed in patients with low or undetectable PD-L1 expression, and conversely, not all patients with high PD-L1 expression respond to therapy.[4] This complexity is compounded by factors such as the dynamic nature of PD-L1 expression, intratumoral heterogeneity, the specific antibody clone used for immunohistochemical detection (e.g., SP142 versus SP263 assays), and the scoring methodologies (e.g., percentage of positive tumor cells versus percentage of tumor area covered by PD-L1-positive immune cells [IC]).[3] The varying PD-L1 testing requirements across different approved indications for Atezolizumab reflect this ongoing effort to refine patient selection strategies and understand the multifaceted role of PD-L1 in mediating treatment response.

4. Pharmacokinetics and Pharmacodynamics

4.1. Pharmacokinetics (PK)

The pharmacokinetic profile of Atezolizumab has been characterized for both intravenous (IV) and subcutaneous (SC) administrations.

Intravenous Administration (Tecentriq®):

Exposure to Atezolizumab increases proportionally with doses ranging from 1 mg/kg to 20 mg/kg, including the standard fixed dose of 1200 mg administered every 3 weeks.15 Steady-state concentrations are typically achieved after 6 to 9 weeks of multiple dosing.15 The systemic accumulation for area under the curve (AUC), maximum concentration (Cmax​), and trough concentration (Ctrough​) are 1.91-fold, 1.46-fold, and 2.75-fold, respectively.16 The central volume of distribution is 3.28 L, and the volume of distribution at steady state (Vss) is 6.91 L in a typical patient.16 Atezolizumab is primarily cleared from circulation via catabolism, typical for monoclonal antibodies, with a clearance (CL) of 0.200 L/day and a terminal elimination half-life (t1/2​) of 27 days.16

Subcutaneous Administration (Tecentriq Hybreza™):

The SC formulation, which includes hyaluronidase-tqjs to enhance dispersion and absorption, demonstrates a mean absolute bioavailability of approximately 72% (CV 83%).13 The median time to reach maximum serum concentration (Tmax​) is 4.5 days (range: 2.2 to 9 days).13 Pharmacokinetic parameters such as Vss (6.9 L) and CL (0.2 L/day), as well as the terminal half-life (27 days), are comparable to the IV formulation.13 Steady-state is also achieved in 6 to 9 weeks, with a systemic accumulation ratio of 2.2 after the approved recommended dosage.13 When comparing SC to IV administration in Study IMscin001, the geometric mean ratio (GMR) for Cycle 1 Ctrough​ was 1.05 (90% CI: 0.88, 1.24) and for AUC0−21days​ was 0.87 (90% CI: 0.83, 0.92). At steady-state, the GMR for Ctrough​ was 1.15 (90% CI: 1.05, 1.26) and for AUC was 1.01 (90% CI: 0.94, 1.08).13 This indicates comparable exposure levels between the two routes of administration, particularly at steady state.

Immunogenicity:

The development of anti-drug antibodies (ADA) is a consideration for biologic therapies. For IV Atezolizumab, ADA incidence ranges from 30% to 42% across various clinical studies.49 While ADA-positive patients exhibited lower systemic Atezolizumab exposure, exploratory analyses in the IMpower150 study showed a similar overall survival (OS) hazard ratio in ADA-positive and ADA-negative subgroups, and the presence of ADA did not increase the incidence or severity of adverse reactions.49

For the SC formulation (Tecentriq Hybreza), the incidence of anti-atezolizumab antibodies was 20% (43/221) during the first year of treatment in Study IMscin001, with 54% (21/39) of these ADA-positive patients developing neutralizing antibodies (NAb).13 Atezolizumab clearance increased by 29% in patients who tested positive for ADA, a change not expected to be clinically significant regarding safety in the initial 6 months of treatment; the effect on long-term effectiveness is unknown.13 The incidence of anti-rHuPH20 antibodies (against the hyaluronidase component) was 5.4%, with no NAbs detected against rHuPH20.13 The availability of a subcutaneous formulation offers enhanced patient convenience, reducing administration time from 30-60 minutes for IV infusion to approximately 7 minutes for SC injection.13 However, the difference in absolute bioavailability (around 72% for SC) and the immunogenicity profile warrant ongoing evaluation, although current data suggest comparable systemic exposure at steady state and no immediate clinically significant impact on pharmacokinetics or safety.

Special Populations:

Pharmacokinetic analyses have shown no clinically significant differences in Atezolizumab exposure based on age (21-89 years), body weight, sex, albumin levels, tumor burden, race/ethnicity, mild or moderate renal impairment, mild or moderate hepatic impairment, PD-L1 expression level, or Eastern Cooperative Oncology Group (ECOG) performance status.13 Therefore, dose adjustments are generally not required for these patient subgroups. Data for patients with severe renal or severe hepatic impairment are limited.16

4.2. Pharmacodynamics (PD)

The exposure-response relationships and the precise time course of pharmacodynamic responses for the safety and effectiveness of Atezolizumab and its co-formulation with hyaluronidase have not been fully characterized.[13] However, studies have indicated that at doses as low as 0.5 µg/kg, approximately 96% saturation of PD-L1 on peripheral blood lymphocytes is achieved, and the distribution of Atezolizumab into tumors increases in a dose-dependent manner.[3] This suggests target engagement at clinically relevant doses. The primary pharmacodynamic effect is the blockade of PD-L1 interaction with PD-1 and B7.1, leading to the restoration of anti-tumor T-cell activity.

5. Regulatory Landscape and Approval History

Atezolizumab, marketed as Tecentriq® and Tecentriq Hybreza™, has undergone extensive regulatory review by major health authorities worldwide, leading to approvals for a range of oncological indications. Its journey reflects both the promise of immune checkpoint inhibition and the rigorous scrutiny applied to new cancer therapies.

5.1. U.S. Food and Drug Administration (FDA)

Genentech, Inc. is the manufacturer responsible for Atezolizumab in the United States.[9]

Initial Approval and Subsequent Expansions:

Atezolizumab first received FDA approval on May 18, 2016, under the Accelerated Approval program, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease had progressed during or following platinum-containing chemotherapy.9

Since its initial approval, Atezolizumab's indications have expanded significantly. Key approvals include:

• Metastatic Non-Small Cell Lung Cancer (NSCLC), second-line plus: October 18, 2016.[9]
• Urothelial Carcinoma (UC), first-line, cisplatin-ineligible: April 17, 2017 (Accelerated Approval).[9]
• Metastatic Non-Squamous NSCLC, first-line combination with bevacizumab, paclitaxel, and carboplatin: December 6, 2018.[9]
• Extensive-Stage Small Cell Lung Cancer (ES-SCLC), first-line combination with carboplatin and etoposide: March 18, 2019.[9]
• PD-L1-positive, unresectable locally advanced or metastatic Triple-Negative Breast Cancer (TNBC), combination with nab-paclitaxel: March 8, 2019 (Accelerated Approval).[9]
• Metastatic Non-Squamous NSCLC, first-line combination with paclitaxel protein-bound and carboplatin: December 3, 2019.[9]
• Metastatic NSCLC, first-line monotherapy for high PD-L1 expression: May 18, 2020.[9]
• Unresectable or metastatic Hepatocellular Carcinoma (HCC), first-line combination with bevacizumab: May 29, 2020.[9]
• BRAF V600 mutation-positive unresectable or metastatic Melanoma, combination with cobimetinib and vemurafenib: July 30, 2020.[9]
• Adjuvant NSCLC, Stage II-IIIA with PD-L1 expression ≥1%: October 15, 2021.[9]
• Unresectable or metastatic Alveolar Soft Part Sarcoma (ASPS), adult and pediatric patients ≥2 years: December 9, 2022.[9]
• Tecentriq Hybreza (subcutaneous formulation): September 12, 2024, for all approved adult IV indications of Tecentriq.[11]

Withdrawals and Updates to Indications:

The regulatory history of Atezolizumab also includes notable withdrawals of indications, primarily due to the failure of confirmatory trials to meet their primary endpoints, a requirement under the FDA's Accelerated Approval Program.

• Urothelial Carcinoma (Prior-Platinum Treatment): The accelerated approval granted in May 2016 for patients with mUC who had progressed after platinum-based chemotherapy (based on IMvigor210 Cohort 2 data) was voluntarily withdrawn by Genentech in March 2021. This decision followed the failure of the confirmatory Phase III IMvigor211 trial to meet its primary endpoint of overall survival (OS) in the PD-L1 high population.[33]
• Triple-Negative Breast Cancer (PD-L1-positive, combination with nab-paclitaxel): The accelerated approval granted in March 2019 for first-line treatment of PD-L1-positive mTNBC (based on progression-free survival benefit in the IMpassion130 trial) was voluntarily withdrawn in the U.S. in August 2021. The decision was made after consultation with the FDA, as the confirmatory Phase III IMpassion131 trial (which used paclitaxel as the chemotherapy backbone instead of nab-paclitaxel) did not meet its primary endpoint of PFS in the PD-L1-positive population. This occurred despite an initial recommendation by the FDA's Oncologic Drugs Advisory Committee (ODAC) to maintain the approval.[33]
• Urothelial Carcinoma (First-Line, Cisplatin-ineligible/PD-L1 positive or Platinum-ineligible regardless of PD-L1 status): The accelerated approval granted in April 2017 (based on IMvigor210 Cohort 1 data) was voluntarily withdrawn by Genentech in November 2022. The confirmatory Phase III IMvigor130 trial did not meet its co-primary endpoint of OS for Atezolizumab plus chemotherapy compared with chemotherapy alone in the first-line treatment of patients with previously untreated advanced bladder cancer.[9]

These withdrawals illustrate the rigorous nature of the FDA's Accelerated Approval pathway, which necessitates robust confirmatory data, typically demonstrating a clinical benefit such as improved OS. The evolving treatment landscape, where new therapeutic options may emerge, can also influence decisions regarding the maintenance of an accelerated approval, reflecting a dynamic, evidence-driven regulatory environment.

Table 2: Current FDA-Approved Indications for Atezolizumab (Tecentriq®/Tecentriq Hybreza™) (as of September 2024)

Indication (Cancer Type, Setting)	Specific Patient Population	Combination Therapy (if any)	Formulation(s)
Non-Small Cell Lung Cancer (NSCLC), Adjuvant	Adult patients with Stage II-IIIA NSCLC following resection and platinum-based chemotherapy; tumors must have PD-L1 expression on ≥1% of tumor cells.	Monotherapy	Tecentriq®, Tecentriq Hybreza™
NSCLC, First-Line Metastatic	Adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥10% of the tumor area); no EGFR or ALK genomic tumor aberrations.	Monotherapy	Tecentriq®, Tecentriq Hybreza™
NSCLC, First-Line Metastatic Non-Squamous	Adult patients with metastatic non-squamous NSCLC; no EGFR or ALK genomic tumor aberrations.	With bevacizumab, paclitaxel, and carboplatin	Tecentriq®, Tecentriq Hybreza™
NSCLC, First-Line Metastatic Non-Squamous	Adult patients with metastatic non-squamous NSCLC; no EGFR or ALK genomic tumor aberrations.	With paclitaxel protein-bound and carboplatin	Tecentriq®, Tecentriq Hybreza™
NSCLC, Metastatic (Previously Treated)	Adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. (Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Atezolizumab).	Monotherapy	Tecentriq®, Tecentriq Hybreza™
Small Cell Lung Cancer (SCLC), First-Line Extensive-Stage	Adult patients with extensive-stage SCLC.	With carboplatin and etoposide	Tecentriq®, Tecentriq Hybreza™
Hepatocellular Carcinoma (HCC), Unresectable or Metastatic	Adult patients with unresectable or metastatic HCC who have not received prior systemic therapy.	With bevacizumab	Tecentriq®, Tecentriq Hybreza™
Melanoma, BRAF V600 Unresectable or Metastatic	Adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.	With cobimetinib and vemurafenib	Tecentriq®, Tecentriq Hybreza™
Alveolar Soft Part Sarcoma (ASPS), Unresectable or Metastatic	Adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS.	Monotherapy	Tecentriq®, Tecentriq Hybreza™

Sources: User Query,.[8]

5.2. European Medicines Agency (EMA)

The Marketing Authorisation Holder for Tecentriq in the European Union is Roche Registration GmbH.[16]

Initial Approval and Subsequent Expansions:

Atezolizumab received its initial marketing authorization valid throughout the EU on September 21, 2017.7 The initial indications at that time included the treatment of adult patients with locally advanced or metastatic NSCLC after prior chemotherapy and locally advanced or metastatic UC after prior platinum-containing chemotherapy, or for those considered cisplatin ineligible whose tumors have a PD-L1 expression ≥ 5%.38

Over time, the EMA has approved Atezolizumab for several other indications, often aligning with, but sometimes differing from, FDA approvals.

• Small Cell Lung Cancer (ES-SCLC), First-Line Combination: Approved around September 2019 in combination with carboplatin and etoposide.[24]
• Triple-Negative Breast Cancer (TNBC), First-Line PD-L1 ≥1% Combination: Approved around August/October 2019 in combination with nab-paclitaxel for unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 ≥1% and who have not received prior chemotherapy for metastatic disease.[27] This indication remains in the EU, unlike its withdrawal in the US.
• Hepatocellular Carcinoma (HCC), First-Line Advanced/Unresectable Combination: Approved around November 2020 in combination with bevacizumab for patients who have not received prior systemic therapy.[26]
• Non-Small Cell Lung Cancer (NSCLC), Adjuvant Early-Stage: Approved for adjuvant treatment following complete resection and platinum-based chemotherapy for adult patients with NSCLC with a high risk of recurrence whose tumors have PD-L1 expression on ≥50% of tumor cells (TC) and who do not have EGFR mutant or ALK-positive NSCLC.[16] This differs slightly in the PD-L1 threshold from the FDA's adjuvant approval (≥1%).
• Non-Small Cell Lung Cancer (NSCLC), First-Line Metastatic Monotherapy: Approved for patients whose tumors have PD-L1 expression ≥50% TC or ≥10% tumor-infiltrating immune cells (IC) and who do not have EGFR-mutant or ALK-positive NSCLC.[16]
• Non-Small Cell Lung Cancer (NSCLC), First-Line Metastatic Combination: Approved in combination with bevacizumab, paclitaxel, and carboplatin for non-squamous NSCLC; and in combination with nab-paclitaxel and carboplatin for non-squamous NSCLC without EGFR/ALK mutations.[16]

Table 3: Current EMA-Approved Indications for Atezolizumab (Tecentriq®) (as of May 2025, based on EPAR summaries)

Indication (Cancer Type, Setting)	Specific Patient Population	Combination Therapy (if any)
Urothelial Carcinoma (UC), Locally Advanced/Metastatic	Adult patients after prior platinum-containing chemotherapy.	Monotherapy
	Adult patients who are considered cisplatin ineligible, AND whose tumors have PD-L1 expression ≥5%.	Monotherapy
NSCLC, Early-Stage Adjuvant	Adult patients with NSCLC with a high risk of recurrence, following complete resection and platinum-based chemotherapy; tumors must have PD-L1 expression on ≥50% TC AND no EGFR mutant or ALK-positive NSCLC.	Monotherapy
NSCLC, First-Line Metastatic Non-Squamous	Adult patients with metastatic non-squamous NSCLC. (For EGFR/ALK+ NSCLC, only after failure of targeted therapies).	With bevacizumab, paclitaxel, and carboplatin
	Adult patients with metastatic non-squamous NSCLC who do not have EGFR mutant or ALK-positive NSCLC.	With nab-paclitaxel and carboplatin
NSCLC, First-Line Metastatic Monotherapy	Adult patients with metastatic NSCLC whose tumors have PD-L1 expression ≥50% TC or ≥10% IC AND who do not have EGFR mutant or ALK-positive NSCLC.	Monotherapy
NSCLC, First-Line Advanced (Platinum-Ineligible)	Adult patients with advanced NSCLC who are ineligible for platinum-based therapy.	Monotherapy
NSCLC, Locally Advanced/Metastatic (Previously Treated)	Adult patients with locally advanced or metastatic NSCLC after prior chemotherapy. (Patients with EGFR/ALK+ NSCLC should also have received targeted therapies).	Monotherapy
SCLC, First-Line Extensive-Stage	Adult patients with extensive-stage SCLC.	With carboplatin and etoposide
TNBC, Unresectable Locally Advanced/Metastatic	Adult patients with unresectable locally advanced or metastatic TNBC whose tumors have PD-L1 expression ≥1% AND who have not received prior chemotherapy for metastatic disease.	With nab-paclitaxel
HCC, Advanced/Unresectable	Adult patients with advanced or unresectable HCC who have not received prior systemic therapy.	With bevacizumab

Sources:.16

Note: Indications for Melanoma and Alveolar Soft Part Sarcoma are approved by the FDA but are not explicitly detailed as current indications in the main EMA EPAR summary documents referenced.22 This highlights potential differences in approval status or reporting timelines between regulatory agencies.

The divergence in approved indications, such as for TNBC (approved in EU with nab-paclitaxel, withdrawn in US) and the differing PD-L1 thresholds for adjuvant NSCLC, underscores that regulatory decisions are complex and can vary based on regional assessments of benefit-risk profiles, confirmatory data availability, and potentially the specifics of the chemotherapy backbone used in combination trials. This necessitates careful consultation of region-specific regulatory information by healthcare providers.

6. Clinical Efficacy and Safety in Approved Indications

Atezolizumab has been evaluated in numerous pivotal clinical trials across various cancer types, leading to its approval for multiple indications. Efficacy is typically assessed using endpoints such as Overall Survival (OS), Progression-Free Survival (PFS), Objective Response Rate (ORR), and Duration of Response (DOR). The safety profile, particularly the occurrence and management of immune-mediated adverse events (irAEs), is a critical aspect of its clinical use. PD-L1 expression serves as an important, albeit imperfect, biomarker for patient selection in several indications.

6.1. Non-Small Cell Lung Cancer (NSCLC)

6.1.1. Adjuvant Treatment (Stage II-IIIA) - IMpower010 (NCT02486718)

The Phase III IMpower010 trial evaluated Atezolizumab as an adjuvant treatment versus Best Supportive Care (BSC) in patients with Stage IB-IIIA NSCLC (Stage II-IIIA for primary FDA/EMA efficacy populations) following complete tumor resection and platinum-based chemotherapy.[15]

Efficacy:

• Primary Endpoint (DFS):
• Stage II-IIIA, PD-L1 TC ≥1% (FDA approval population): Atezolizumab demonstrated a statistically significant improvement in DFS compared to BSC (Hazard Ratio 0.66; 95% CI 0.50, 0.88; p=0.0039/0.004).[15] At a median follow-up of 32.2 months, median DFS was not reached for Atezolizumab vs 35.3 months for BSC [[15] (referencing Felip et al., Lancet 2021)]. The 5-year DFS rates in the Stage II-IIIA population were 49.3% for Atezolizumab and 44.4% for BSC (overall population, not PD-L1 specific in this snippet).[67]
• Stage II-IIIA, PD-L1 TC ≥50% (EMA approval population): The greatest DFS benefit was observed in this subgroup, with Atezolizumab reducing the risk of disease recurrence or death by 57% (unstratified HR 0.43; 95% CI 0.27, 0.68).[29] Median DFS was not reached for Atezolizumab vs 37.2 months for BSC [[15] (referencing Felip et al., Lancet 2021)]. The 5-year DFS rate was 65.1% for Atezolizumab vs 44.5% for BSC in this subgroup.[68]
• All Randomized Stage II-IIIA: Atezolizumab also showed a significant DFS improvement (HR 0.79; 95% CI 0.64, 0.96; p=0.0205).[42] Median DFS was 42.3 months for Atezolizumab vs 35.3 months for BSC.[42]
• Overall Survival (OS):
• Data were immature at the time of primary DFS analysis.
• Stage II-IIIA, PD-L1 TC ≥1%: An emerging trend towards OS improvement favored Atezolizumab (stratified HR 0.71; 95% CI 0.49, 1.03 at April 2022 CCOD [69]; HR 0.77; 95% CI 0.56, 1.06 at 5-year follow-up [67]). Median OS was not reached for Atezolizumab vs 87.1 months for BSC.[67] 5-year OS rates were 74.8% vs 66.3%.[67]
• Stage II-IIIA, PD-L1 TC ≥50%: A strong OS trend favored Atezolizumab (unstratified HR 0.47; 95% CI 0.28, 0.77 at 5-year follow-up).[68] Median OS was not reached for Atezolizumab vs 87.1 months for BSC.[68] 5-year OS rates were 82.7% vs 65.3%.[68]

Safety:

The safety profile of Atezolizumab in IMpower010 was consistent with its known safety profile in the metastatic setting.29 No new safety signals were identified.43 Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 21.8% of patients receiving Atezolizumab versus 11.5% receiving BSC (control arm adverse events are generally low as it is supportive care) [15 (referencing Felip et al., Lancet 2021)]. Adverse events leading to discontinuation of Atezolizumab occurred in 18.2% of patients [15 (referencing Felip et al., Lancet 2021)].

Table 4: IMpower010 Efficacy & Safety Summary (Adjuvant NSCLC)

Endpoint	Population	Atezolizumab arm	BSC arm	Hazard Ratio (95% CI)	p-value	Reference(s)
Median DFS	Stage II-IIIA PD-L1 TC ≥1%	Not Reached	35.3 months	0.66 (0.50, 0.88)	0.0039	15
	Stage II-IIIA PD-L1 TC ≥50%	Not Reached	37.2 months	0.43 (0.27, 0.68) (unstratified)	--	15
5-Year DFS Rate	Stage II-IIIA	49.3%	44.4%	0.83 (0.69, 1.00) (stratified, overall Stage II-IIIA)	--	67
	Stage II-IIIA PD-L1 TC ≥50%	65.1%	44.5%	0.48 (0.32, 0.72)	--	68
Median OS	Stage II-IIIA PD-L1 TC ≥1%	Not Reached	87.1 months	0.77 (0.56, 1.06)	-- (trend)	67
	Stage II-IIIA PD-L1 TC ≥50%	Not Reached	87.1 months	0.47 (0.28, 0.77) (unstratified)	-- (trend)	68
5-Year OS Rate	Stage II-IIIA PD-L1 TC ≥1%	74.8%	66.3%	--	--	67
	Stage II-IIIA PD-L1 TC ≥50%	82.7%	65.3%	--	--	68
Grade 3/4 TRAEs	All treated	21.8%	11.5%	--	--	15 (referencing Felip et al., Lancet 2021)
AEs leading to Discontinuation	All treated	18.2%	N/A	--	--	15 (referencing Felip et al., Lancet 2021)

DFS: Disease-Free Survival; OS: Overall Survival; BSC: Best Supportive Care; TC: Tumor Cell; HR: Hazard Ratio; CI: Confidence Interval; N/A: Not Applicable. OS data are from interim/exploratory analyses and should be interpreted with caution.

The IMpower010 trial established Atezolizumab as an important adjuvant therapy option for patients with resected early-stage NSCLC, particularly those with PD-L1 expression, aiming to reduce the risk of disease recurrence and improve the chances of cure. The differing PD-L1 thresholds for FDA and EMA approvals reflect nuanced interpretations of subgroup benefits.

6.1.2. First-Line Metastatic NSCLC (High PD-L1 Expression, Monotherapy) - IMpower110 (NCT02409342)

The Phase III IMpower110 trial compared Atezolizumab monotherapy with platinum-based chemotherapy as first-line treatment for patients with metastatic NSCLC selected for PD-L1 expression (TC ≥1% or IC ≥1% by SP142 assay), without EGFR or ALK genomic tumor aberrations.[40]

Efficacy (PD-L1 High WT population):

• Overall Survival (OS):
• Primary analysis (median follow-up 15.7 months): Median OS was 20.2 months for Atezolizumab versus 13.1 months for chemotherapy (HR 0.59; 95% CI 0.40, 0.89; p=0.0106).[17]
• Updated analysis (median follow-up 31.3 months): Median OS was 20.2 months for Atezolizumab versus 14.7 months for chemotherapy (HR 0.76; 95% CI 0.54, 1.09).[17]
• Progression-Free Survival (PFS):
• Primary analysis: Median PFS was 8.1 months for Atezolizumab versus 5.0 months for chemotherapy (HR 0.63; 95% CI 0.45, 0.88).[72]
• Objective Response Rate (ORR):
• Primary analysis: ORR was 38% for Atezolizumab versus 29% for chemotherapy.[72]
• Duration of Response (DOR):
• Updated analysis (PD-L1 high or intermediate): Median DOR was 38.9 months for Atezolizumab versus 5.8 months for chemotherapy.[41]

Safety:

Atezolizumab monotherapy was associated with a more favorable safety profile compared to chemotherapy.

• Grade 3-4 treatment-related AEs were reported in 12.9% of patients receiving Atezolizumab compared with 44.1% receiving chemotherapy.[17] Another report cited 30.1% vs 52.5%.[40]
• All-cause AEs that were more frequent with chemotherapy included anemia, nausea, neutropenia, constipation, thrombocytopenia, vomiting, and alopecia. AEs more frequent with Atezolizumab included pyrexia, increased AST, rash, nasopharyngitis, arthralgia, pruritus, and hypothyroidism.[41] No new or unexpected toxicities were observed.[41]

Table 5: IMpower110 Efficacy & Safety Summary (First-Line Metastatic NSCLC, PD-L1 High)

Endpoint	Atezolizumab arm	Chemotherapy arm	Hazard Ratio (95% CI)	p-value	Reference(s)
Median OS (Primary)	20.2 months	13.1 months	0.59 (0.40, 0.89)	0.0106	17
Median OS (Updated)	20.2 months	14.7 months	0.76 (0.54, 1.09)	--	17
Median PFS (Primary)	8.1 months	5.0 months	0.63 (0.45, 0.88)	--	72
ORR (Primary)	38%	29%	--	--	72
Median DOR (Updated, PD-L1 High/Intermediate)	38.9 months	5.8 months	--	--	41
Grade 3/4 TRAEs	12.9% - 30.1%	44.1% - 52.5%	--	--	17

OS: Overall Survival; PFS: Progression-Free Survival; ORR: Objective Response Rate; DOR: Duration of Response; TRAEs: Treatment-Related Adverse Events; WT: Wild-Type (EGFR/ALK negative).

IMpower110 established Atezolizumab monotherapy as a first-line standard of care for patients with metastatic NSCLC and high PD-L1 expression, offering a survival advantage and a better tolerability profile compared to traditional chemotherapy.

6.1.3. First-Line Metastatic Non-Squamous NSCLC (Combination with Bevacizumab + Paclitaxel + Carboplatin) - IMpower150 (NCT02366143)

The Phase III IMpower150 trial evaluated Atezolizumab in combination with bevacizumab and chemotherapy (paclitaxel + carboplatin) (ABCP regimen) versus bevacizumab plus chemotherapy (BCP regimen) in chemotherapy-naïve patients with metastatic non-squamous NSCLC.[49] The trial included an arm with Atezolizumab + chemotherapy (ACP) as well.

Efficacy (ABCP vs BCP in ITT-WT population):

• Overall Survival (OS): Median OS was 19.2 months for ABCP versus 14.7 months for BCP (HR 0.78; 95% CI 0.64, 0.96; p=0.0164).[49] Final OS analysis confirmed this benefit.[74]
• Progression-Free Survival (PFS): Median PFS was 8.5 months for ABCP versus 7.0 months for BCP (HR 0.71; 95% CI 0.59, 0.85; p=0.0002).[49] The initial report showed median PFS of 8.3 months vs 6.8 months (HR 0.62; p<0.001) [[75] (refers to Socinski et al NEJM 2018)].
• Objective Response Rate (ORR): ORR was 55% for ABCP versus 42% for BCP.[49]
• Subgroup Analyses: OS benefit with ABCP was observed across PD-L1 expression subgroups, including PD-L1 negative patients.[76] Notably, benefit was also suggested in exploratory analyses of patients with baseline liver metastases (median OS 13.2 vs 9.1 months; HR 0.54) and those with EGFR/ALK genomic alterations after failure of TKI therapy (median OS Not Reached vs 17.5 months; HR 0.54).[74]

Safety (ABCP regimen):

The most common adverse reactions (≥20%) were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy.13 Atezolizumab was discontinued due to adverse reactions in 15% of patients, with pneumonitis being the most common reason (1.8%).49

Table 6: IMpower150 Efficacy & Safety Summary (ABCP vs BCP in First-Line Metastatic Non-Squamous NSCLC, ITT-WT)

Endpoint	Atezolizumab + Bev + Chemo (ABCP)	Bev + Chemo (BCP)	Hazard Ratio (95% CI)	p-value	Reference(s)
Median OS	19.2 months	14.7 months	0.78 (0.64, 0.96)	0.0164	49
Median PFS	8.5 months	7.0 months	0.71 (0.59, 0.85)	0.0002	49
ORR	55%	42%	--	--	49
Most Common AEs (≥20%) with ABCP	\multicolumn{4}{l	}{Fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, neuropathy}	13
Atezo Discontinuation due to AEs	\multicolumn{4}{l	}{15% (Pneumonitis 1.8%)}	49

Bev: Bevacizumab; Chemo: Paclitaxel + Carboplatin; ITT-WT: Intent-to-Treat Wild-Type (EGFR/ALK negative).

IMpower150 demonstrated that the addition of Atezolizumab to bevacizumab and chemotherapy provided a significant survival benefit for patients with metastatic non-squamous NSCLC, including in PD-L1 low/negative populations and those with challenging prognostic features like liver metastases, establishing a new first-line treatment option.

6.1.4. First-Line Metastatic Non-Squamous NSCLC (Combination with Carboplatin + Nab-Paclitaxel) - IMpower130 (NCT02367781)

The Phase III IMpower130 trial compared Atezolizumab plus chemotherapy (carboplatin and nab-paclitaxel) with chemotherapy alone as first-line treatment for metastatic non-squamous NSCLC, irrespective of PD-L1 status and in patients without EGFR/ALK mutations (ITT-WT population).[44]

Efficacy (ITT-WT population):

• Overall Survival (OS): Median OS was 18.6 months for Atezolizumab plus chemotherapy versus 13.9 months for chemotherapy alone (stratified HR 0.79; 95% CI 0.64, 0.98; p=0.033).[44]
• Progression-Free Survival (PFS): Median PFS was 7.0 months for Atezolizumab plus chemotherapy versus 5.5 months for chemotherapy alone (HR 0.64; 95% CI 0.54, 0.77; p<0.0001).[44]
• Objective Response Rate (ORR): ORR was 49.2% with the Atezolizumab regimen versus 31.9% with chemotherapy alone (p=0.0004).[45]
• Duration of Response (DOR): Median DOR was 8.4 months versus 6.1 months, respectively.[45]
• Subgroup Analyses: PFS benefit was observed across PD-L1 expression subgroups (high, low, negative). OS benefit was also seen across these subgroups, though the HR for PD-L1 high was 0.84.[45] Patients with liver metastases did not appear to benefit in PFS or OS from this combination.[45]

Safety:

• Grade 3 or worse treatment-related AEs occurred in 73.2% of patients in the Atezolizumab plus chemotherapy group versus 60.3% in the chemotherapy group.[45]
• The most common Grade 3+ TRAEs were neutropenia (32% vs 28%), anemia (29% vs 20%), and decreased neutrophil count (12% vs 8%).[44]
• Treatment-related serious AEs were reported in 24% versus 13% of patients, respectively.[44] Treatment-related deaths occurred in 2% vs <1%.[44]

Table 7: IMpower130 (NSCLC) Efficacy & Safety Summary (First-Line Metastatic Non-Squamous NSCLC, ITT-WT)

Endpoint	Atezolizumab + Chemo	Chemo Alone	Hazard Ratio (95% CI)	p-value	Reference(s)
Median OS	18.6 months	13.9 months	0.79 (0.64, 0.98)	0.033	44
Median PFS	7.0 months	5.5 months	0.64 (0.54, 0.77)	<0.0001	44
ORR	49.2%	31.9%	--	0.0004	45
Median DOR	8.4 months	6.1 months	--	--	45
Grade 3/4 TRAEs	73.2%	60.3%	--	--	45

Chemo: Carboplatin + nab-paclitaxel; ITT-WT: Intent-to-Treat Wild-Type (EGFR/ALK negative).

The IMpower130 trial provided another effective first-line chemo-immunotherapy option for patients with metastatic non-squamous NSCLC, demonstrating significant improvements in OS and PFS.

6.1.5. Second-Line+ Metastatic NSCLC (Monotherapy) - OAK (NCT02008227) & POPLAR (NCT01903993)

The Phase III OAK and Phase II POPLAR trials evaluated Atezolizumab monotherapy versus docetaxel in patients with locally advanced or metastatic NSCLC who had progressed on or after platinum-containing chemotherapy.[77]

Efficacy:

• Overall Survival (OS) - OAK Trial: Median OS was 13.3 months for Atezolizumab versus 9.8 months for docetaxel (HR 0.78; 95% CI 0.68, 0.89).[77] The 4-year OS rate was 15.5% for Atezolizumab versus 8.7% for docetaxel.[77]
• Overall Survival (OS) - POPLAR Trial: Median OS was 12.6 months for Atezolizumab versus 9.7 months for docetaxel (HR 0.76; 95% CI 0.58, 1.00).[77] The 4-year OS rate was 14.8% for Atezolizumab versus 8.1% for docetaxel.[77]
• Subgroup Analyses: Atezolizumab demonstrated an OS benefit compared with docetaxel across all PD-L1 expression subgroups (including TC0/IC0) and histology types (squamous and non-squamous) in both trials.[77]
• Long-term Survivors: Most 4-year survivors in the docetaxel arms had received subsequent immunotherapy (50% in POPLAR, 65% in OAK).[77]

Safety:

Atezolizumab had a more favorable safety profile compared to docetaxel.

• Treatment-related Grade 3/4 AEs were less frequent with Atezolizumab. In 4-year survivors, these occurred in 16% (OAK) and 27% (POPLAR) of Atezolizumab-treated patients.[77]
• No new safety signals were identified with long-term follow-up.[77] The TAIL study (Phase III/IV, NCT03285763), evaluating atezolizumab in a broader population including those often excluded from pivotal trials, showed a similar risk-benefit profile, with TR SAEs in 8.0% and TR irAEs in 9.4%.[78]

Table 8: OAK & POPLAR Trials Efficacy & Safety Summary (Second-Line+ Metastatic NSCLC)

Trial	Endpoint	Atezolizumab arm	Docetaxel arm	Hazard Ratio (95% CI)	Reference(s)
OAK	Median OS	13.3 months	9.8 months	0.78 (0.68, 0.89)	77
	4-Year OS Rate	15.5%	8.7%	--	77
POPLAR	Median OS	12.6 months	9.7 months	0.76 (0.58, 1.00)	77
	4-Year OS Rate	14.8%	8.1%	--	77
Safety (OAK & POPLAR)	Grade 3/4 TRAEs (4-yr survivors)	16% (OAK), 27% (POPLAR)	N/A	--	77

OS: Overall Survival; TRAEs: Treatment-Related Adverse Events; N/A: Not Applicable for docetaxel arm in this specific long-term survivor analysis.

The OAK and POPLAR trials were instrumental in establishing Atezolizumab as a standard second-line treatment for metastatic NSCLC, demonstrating improved survival and better tolerability than chemotherapy, irrespective of PD-L1 status.

6.2. Small Cell Lung Cancer (SCLC)

6.2.1. First-Line Extensive-Stage SCLC (Combination with Carboplatin + Etoposide) - IMpower133 (NCT02763579)

The Phase III IMpower133 trial evaluated Atezolizumab in combination with chemotherapy (carboplatin and etoposide) versus placebo plus chemotherapy as first-line treatment for patients with extensive-stage SCLC (ES-SCLC).[24]

Efficacy:

• Overall Survival (OS):
• Primary analysis (median follow-up 13.9 months): Median OS was 12.3 months for Atezolizumab plus chemotherapy versus 10.3 months for placebo plus chemotherapy (HR 0.70; 95% CI 0.54, 0.91; p=0.0069).[24]
• Updated OS analysis (median follow-up 22.9 months): Median OS was 12.3 months versus 10.3 months (HR 0.76; 95% CI 0.60, 0.95; p=0.0154).[81]
• Five-year survival data from the IMbrella A extension study showed continued OS benefit.[84]
• Progression-Free Survival (PFS):
• Primary analysis: Median PFS was 5.2 months for Atezolizumab plus chemotherapy versus 4.3 months for placebo plus chemotherapy (HR 0.77; 95% CI 0.62, 0.96; p=0.0170).[24]
• Objective Response Rate (ORR): ORR was similar between the arms: 60% with Atezolizumab plus chemotherapy versus 64% with placebo plus chemotherapy.[82]

Safety:

The safety profile of the Atezolizumab combination was generally consistent with the known profiles of the individual agents.

• Grade 3-4 adverse events occurred in 56.6% of patients in the Atezolizumab plus chemotherapy arm and 56.1% in the placebo plus chemotherapy arm.[24]
• The most common Grade 3-4 AEs (≥10%) in the Atezolizumab arm were neutropenia (23%), anemia (14%), and decreased neutrophil count (14%).[24]
• The MAURIS Phase IIIb trial, evaluating this combination in a real-world-like setting, showed serious AEs in 29.9% and irAEs in 14.9%, with no new safety signals.[83]

Table 9: IMpower133 Efficacy & Safety Summary (First-Line ES-SCLC)

Endpoint	Atezolizumab + Chemo	Placebo + Chemo	Hazard Ratio (95% CI)	p-value	Reference(s)
Median OS (Primary)	12.3 months	10.3 months	0.70 (0.54, 0.91)	0.0069	24
Median OS (Updated)	12.3 months	10.3 months	0.76 (0.60, 0.95)	0.0154	81
Median PFS (Primary)	5.2 months	4.3 months	0.77 (0.62, 0.96)	0.0170	24
ORR	60%	64%	--	--	82
Grade 3/4 AEs	56.6%	56.1%	--	--	24

Chemo: Carboplatin + Etoposide.

The IMpower133 trial represented a significant advancement in the first-line treatment of ES-SCLC, establishing chemo-immunotherapy with Atezolizumab as a new standard of care by demonstrating an OS benefit for the first time in over two decades for this aggressive disease.[24]

6.3. Hepatocellular Carcinoma (HCC)

6.3.1. First-Line Unresectable/Metastatic HCC (Combination with Bevacizumab) - IMbrave150 (NCT03434379)

The Phase III IMbrave150 trial compared Atezolizumab plus bevacizumab with sorafenib in patients with unresectable HCC who had not received prior systemic therapy.[26]

Efficacy:

• Overall Survival (OS):
• Primary analysis (median follow-up 8.6 months): Median OS was not reached for Atezolizumab plus bevacizumab versus 13.2 months for sorafenib (HR 0.58; 95% CI 0.42, 0.79; p<0.001) [[86] (refers to Finn NEJM 2020), [90]]. OS at 12 months was 67.2% vs 54.6%.[90]
• Updated analysis (median follow-up 15.6 months): Median OS was 19.2 months for Atezolizumab plus bevacizumab versus 13.4 months for sorafenib (HR 0.66; 95% CI 0.52, 0.85; p=0.0009).[86] Survival at 18 months was 52% vs 40%.[88]
• Progression-Free Survival (PFS) (Independent Review Facility-assessed per RECIST 1.1):
• Primary analysis: Median PFS was 6.8 months for Atezolizumab plus bevacizumab versus 4.3 months for sorafenib (HR 0.59; 95% CI 0.47, 0.76; p<0.001) [[26] (refers to Finn NEJM 2020), [90]].
• Objective Response Rate (ORR) (IRF-assessed per RECIST 1.1):
• Updated analysis: ORR was 29.8% for Atezolizumab plus bevacizumab (including 7.7% Complete Response) versus 11.3% for sorafenib (CR 0%).[88]
• Patient-Reported Outcomes (PROs): Atezolizumab plus bevacizumab resulted in a longer time to deterioration of patient-reported quality of life and functioning compared to sorafenib.[90]

Safety:

• Grade 3 or 4 adverse events occurred in 56.5% of patients receiving Atezolizumab plus bevacizumab and 55.1% of patients receiving sorafenib.[90]
• Hypertension was a notable Grade 3/4 AE in the combination arm (15.2%).[90]
• Serious AEs were recorded in 38% of patients in the combination arm.[90] The safety profile was consistent with the known profiles of the individual drugs, with no new unexpected safety signals.[88] Management of AEs of special interest (AESIs) was outlined.[91]

Table 10: IMbrave150 Efficacy & Safety Summary (First-Line Unresectable HCC)

Endpoint	Atezolizumab + Bevacizumab	Sorafenib	Hazard Ratio (95% CI)	p-value	Reference(s)
Median OS (Updated)	19.2 months	13.4 months	0.66 (0.52, 0.85)	0.0009	86
Median PFS (Primary, IRF)	6.8 months	4.3 months	0.59 (0.47, 0.76)	<0.001	26 (refers to Finn NEJM 2020), 90
ORR (Updated, IRF)	29.8% (7.7% CR)	11.3% (0% CR)	--	--	88
Grade 3/4 AEs	56.5%	55.1%	--	--	90
Grade 3/4 Hypertension	15.2%	Not specified	--	--	90

The IMbrave150 trial established Atezolizumab in combination with bevacizumab as a new standard of care for the first-line treatment of unresectable HCC, demonstrating superior OS and PFS compared to sorafenib, along with a manageable safety profile and better preservation of quality of life. This was a landmark achievement, being the first regimen in over a decade to show such benefits in this setting.[26]

6.4. Melanoma

6.4.1. BRAF V600 Mutation-Positive Unresectable/Metastatic Melanoma (Combination with Cobimetinib + Vemurafenib) - IMspire150 (NCT02908672)

The Phase III IMspire150 trial evaluated the addition of Atezolizumab to targeted therapy (cobimetinib [MEK inhibitor] + vemurafenib) versus placebo plus cobimetinib and vemurafenib in patients with previously untreated BRAF V600 mutation-positive unresectable or metastatic melanoma.[54]

Efficacy:

• Progression-Free Survival (PFS) (Investigator-assessed, Primary Endpoint): Median PFS was 15.1 months for the Atezolizumab triplet combination versus 10.6 months for the placebo triplet combination (HR 0.78; 95% CI 0.63, 0.97; p=0.0249).[54]
• Overall Survival (OS) (Second Interim Analysis): Median OS was 39.0 months in the Atezolizumab group versus 25.8 months in the control group (HR 0.84; 95% CI 0.66, 1.06; p=0.14). This difference was not statistically significant at this analysis point, though a late separation of survival curves favoring the Atezolizumab group was observed.[92] Final OS analysis is awaited.
• Objective Response Rate (ORR): Not explicitly detailed in the provided summaries for the primary publication, but the FDA approval was based on PFS.

Safety:

The safety profile of the Atezolizumab combination was consistent with the known safety profiles of the individual medicines.55

• The most common adverse events (≥20%) with Atezolizumab plus cobimetinib and vemurafenib included rash, musculoskeletal pain, fatigue, hepatotoxicity, pyrexia, nausea, pruritus, edema, stomatitis, hypothyroidism, and photosensitivity reaction.[54]
• Grade 3 or 4 AEs occurred in 75% of the Atezolizumab group versus 66% of the control group.[92] The most common Grade 3-4 AEs were increased lipase, increased creatine phosphokinase, and increased alanine aminotransferase.[93]
• Serious AEs were reported in 48% versus 42% of patients, respectively. Adverse events led to discontinuation of all study treatment in 15% vs 16%.[92] Grade 5 AEs occurred in 3% vs 2%.[93]

Table 11: IMspire150 Efficacy & Safety Summary (First-Line BRAF V600+ Metastatic Melanoma)

Endpoint	Atezolizumab + Cobi + Vem	Placebo + Cobi + Vem	Hazard Ratio (95% CI)	p-value	Reference(s)
Median PFS	15.1 months	10.6 months	0.78 (0.63, 0.97)	0.0249	54
Median OS (Interim)	39.0 months	25.8 months	0.84 (0.66, 1.06)	0.14	92
Grade 3/4 AEs	75%	66%	--	--	92
Serious AEs	48%	42%	--	--	92

Cobi: Cobimetinib; Vem: Vemurafenib.

The IMspire150 trial demonstrated a statistically significant improvement in PFS with the addition of Atezolizumab to BRAF/MEK targeted therapy for BRAF V600-mutant melanoma. While the OS benefit was not statistically significant at the interim analysis, the trial contributed to the FDA approval of this triplet regimen.

6.5. Alveolar Soft Part Sarcoma (ASPS)

6.5.1. Unresectable/Metastatic ASPS (Adult & Pediatric ≥2 years, Monotherapy) - Study ML39345 / APECS (NCT03141684)

This open-label, single-arm, multicenter Phase II study evaluated Atezolizumab monotherapy in patients aged 2 years and older with unresectable or metastatic ASPS.[56] ASPS is an ultra-rare sarcoma with limited treatment options.[95]

Efficacy:

• Objective Response Rate (ORR) (Independent Review Committee, RECIST 1.1):
• FDA report: ORR was 24% (12/49 patients; 95% CI 13, 39).[56]
• Wagner et al. (NEJM 2023, N=52): ORR was 37% (19 partial responses, 1 complete response).[95] An earlier ASCO abstract (N=43 evaluable) reported ORR of 37.2% (1 CR, 15 PRs).[94]
• Duration of Response (DOR):
• FDA report: Of the 12 responders, 67% had a DOR ≥6 months, and 42% had a DOR ≥12 months.[56]
• ASCO abstract: Median DOR was 16.5 months (range, 4.9–38.1 months).[94]
• Disease Control:
• Wagner et al. (NEJM 2023): 30 out of 33 non-responding patients had stable disease (SD).[96]
• ASCO abstract: SD was present in 58.1% (25/43).[94]
• Time to Response: Median time to confirmed response was 3.5 months (range, 2.1–14.9 months).[94] Some patients took over a year to respond.[96]

Safety:

Atezolizumab was generally well-tolerated.

• The most common adverse reactions (≥15% in FDA report) were musculoskeletal pain (67%), fatigue (55%), rash (47%), cough (45%), nausea (43%), headache (43%), hypertension (43%), vomiting (37%), constipation (33%), dyspnea (33%), dizziness (29%), hemorrhage (29%), insomnia (27%), diarrhea (27%), pyrexia, anxiety, and abdominal pain.[56]
• ASCO abstract reported Grade 3 AEs potentially related to Atezolizumab in 16.3% of patients (7/43), including diarrhea, hypothyroidism, transaminitis, anemia, vertigo, extremity pain, myalgia, pneumonitis, rash, and stroke (n=1 each). No Grade 4 or 5 events were reported at that time.[94]
• NEJM 2023 report: Side effects were mostly mild; nobody discontinued treatment due to side effects.[96]

Table 12: Study ML39345/APECS Efficacy & Safety Summary (ASPS)

Endpoint	Result (FDA Report, N=49)	Result (Wagner et al. NEJM 2023, N=52)	Result (ASCO 2021 Abstract, N=43 eval.)	Reference(s)
ORR (IRC, RECIST 1.1)	24% (95% CI: 13, 39)	37% (1 CR, 19 PR)	37.2% (1 CR, 15 PR)	56
DOR ≥6 months	67% of responders	--	--	56
DOR ≥12 months	42% of responders	--	--	56
Median DOR	--	--	16.5 months	94
Stable Disease Rate	--	30/33 non-responders	58.1%	94
Most Common AEs (≥15%)	\multicolumn{3}{l	}{Musculoskeletal pain, fatigue, rash, cough, nausea, headache, hypertension}	56
Grade 3 Related AEs	--	Mostly mild side effects reported	16.3%	94

This trial led to the first FDA approval of a therapy for advanced ASPS, a significant milestone for this rare cancer, demonstrating durable responses and a manageable safety profile with Atezolizumab monotherapy.[57]

6.6. Urothelial Carcinoma (UC) – Including Withdrawal Details

Atezolizumab initially received accelerated approvals for metastatic urothelial carcinoma (mUC) in both second-line+ and first-line cisplatin-ineligible settings. However, these indications were later voluntarily withdrawn in the U.S. after confirmatory trials did not meet their primary endpoints. The EMA approvals for certain UC populations persist.

Second-Line+ mUC (Post-Platinum):

• IMvigor210 Cohort 2 (NCT02108652): This Phase II study supported the initial FDA accelerated approval (May 2016) and EMA approval.[22]
• Efficacy (Final Analysis, median follow-up 46.2 months):
• ORR (RECIST 1.1, IRF): 16.5% in all comers; 27.0% in PD-L1 IC2/3 (high expression). CR rates were 7.1% and 14.0%, respectively.[98]
• Median OS: 7.9 months in all comers; 11.9 months in PD-L1 IC2/3.[98]
• 4-year OS rates: 15.3% in all comers; 30.3% in PD-L1 IC2/3.[98]
• Median DOR (IRF): 24.8 months in all comers; 29.7 months in PD-L1 IC2/3.[98]
• Safety: Treatment-related Grade 3/4 AEs occurred in 18.7% of patients. No new safety signals with long-term follow-up.[98]
• Confirmatory Trial - IMvigor211 (NCT02302807): This Phase III trial compared Atezolizumab to chemotherapy (vinflunine, paclitaxel, or docetaxel) in patients with mUC who progressed after platinum-based therapy.
• The trial missed its primary endpoint of OS in the PD-L1 high (IC2/3) population (announced May 2017).[58]
• This failure led to the voluntary withdrawal of the U.S. indication for prior-platinum treated mUC in March 2021.[33]

First-Line mUC (Cisplatin-Ineligible):

• IMvigor210 Cohort 1 (NCT02108652): This cohort supported the FDA accelerated approval (April 2017) for cisplatin-ineligible patients and the EMA approval for cisplatin-ineligible patients with PD-L1 expression ≥5%.[22]
• Efficacy (Final Analysis, median follow-up 96.4 months):
• ORR (RECIST 1.1, IRF): 23.5% in all comers; 28.1% in PD-L1 IC2/3. CR rates were 10.1% and 15.6%, respectively.[98]
• Median OS: 16.3 months in all comers; 12.3 months in PD-L1 IC2/3.[98]
• 5-year OS rates: 21.6% in all comers; 27.0% in PD-L1 IC2/3.[98]
• Median DOR (IRF): 59.1 months in all comers; 93.8 months in PD-L1 IC2/3.[98]
• Safety: Treatment-related Grade 3/4 AEs occurred in 21.8%; one treatment-related death (sepsis).[98]
• Confirmatory Trial - IMvigor130 (NCT02807636): This Phase III trial evaluated Atezolizumab plus platinum-based chemotherapy versus chemotherapy alone, and Atezolizumab monotherapy versus chemotherapy alone, in previously untreated patients with locally advanced or mUC.
• The Atezolizumab plus chemotherapy arm failed to meet its co-primary endpoint of OS compared to chemotherapy alone.[33]
• This outcome led to the voluntary withdrawal of the U.S. indication for first-line cisplatin-ineligible mUC (both PD-L1 positive and platinum-ineligible regardless of PD-L1 status) in November 2022.[9]

The regulatory journey of Atezolizumab in urothelial carcinoma underscores the challenges of translating efficacy from early-phase, single-arm studies into confirmed benefits in larger, randomized Phase III trials. While durable responses were seen in a subset of patients in IMvigor210, the failure of IMvigor211 and IMvigor130 to meet their OS endpoints in the specified populations, coupled with an evolving treatment landscape, led to the U.S. withdrawals. However, EMA approvals for certain UC populations persist based on their own benefit-risk assessments.

6.7. Triple-Negative Breast Cancer (TNBC) – Including Withdrawal Details (FDA)

6.7.1. First-Line Metastatic TNBC (PD-L1 IC ≥1%, Combination with Nab-Paclitaxel) - IMpassion130 (NCT02425891)

The Phase III IMpassion130 trial evaluated Atezolizumab in combination with nab-paclitaxel versus placebo plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic TNBC.[27]

Efficacy:

• Progression-Free Survival (PFS):
• PD-L1 IC ≥1% population: Median PFS was 7.5 months for Atezolizumab plus nab-paclitaxel versus 5.0 months for placebo plus nab-paclitaxel (HR 0.62; 95% CI 0.49, 0.78; p<0.001).[100] This was a primary endpoint and met statistical significance.
• Intent-to-Treat (ITT) population: Median PFS was 7.2 months versus 5.5 months (HR 0.80; 95% CI 0.69, 0.92; p=0.002).[99]
• Overall Survival (OS):
• PD-L1 IC ≥1% population: At the second interim analysis, a clinically meaningful OS improvement of 7 to 9.5 months was observed (median OS ~25.0 months for Atezolizumab combo vs ~15.5-18.0 months for placebo combo; HR ~0.62-0.71).[27] However, statistical significance was not formally achieved due to hierarchical testing. Final OS analysis showed a median OS of 25.4 months vs 17.9 months (HR 0.67; 95% CI: 0.53, 0.86).[99]
• ITT population: At interim analysis, median OS was 21.3 months versus 17.6 months (HR 0.84; 95% CI 0.69, 1.02; p=0.0840), which was not statistically significant.[99]
• Objective Response Rate (ORR) (PD-L1 IC ≥1%): 58.9% for Atezolizumab combo versus 42.6% for placebo combo.[100]

Regulatory Status:

• FDA: Granted accelerated approval in March 2019 based on PFS benefit in the PD-L1+ population.[9] However, this indication was voluntarily withdrawn in the U.S. in August 2021. The confirmatory trial, IMpassion131 (NCT03125902), which used paclitaxel instead of nab-paclitaxel as the chemotherapy backbone, did not meet its primary endpoint of PFS in the PD-L1-positive population.[36] Despite an initial ODAC vote to maintain approval, the FDA later reconsidered, leading to the withdrawal.[36]
• EMA: Granted approval in August/October 2019 for Atezolizumab in combination with nab-paclitaxel for PD-L1 IC ≥1% mTNBC, and this approval remains.[16]

Safety:

The safety profile was consistent with the known profiles of each agent.100 Adverse events of special interest (irAEs) were more common with the Atezolizumab combination. Common AEs with increased frequency in the Atezolizumab arm included nausea, cough, neutropenia, pyrexia, and hypothyroidism.100

Table 13: IMpassion130 Efficacy & Safety Summary (First-Line Metastatic TNBC)

Endpoint	Population	Atezolizumab + Nab-Paclitaxel	Placebo + Nab-Paclitaxel	Hazard Ratio (95% CI)	p-value	Reference(s)
Median PFS	PD-L1 IC ≥1%	7.5 months	5.0 months	0.62 (0.49, 0.78)	<0.001	100
	ITT	7.2 months	5.5 months	0.80 (0.69, 0.92)	0.002	99
Median OS (Final)	PD-L1 IC ≥1%	25.4 months	17.9 months	0.67 (0.53, 0.86)	--	99
Median OS (Interim)	ITT	21.3 months	17.6 months	0.84 (0.69, 1.02)	0.0840	99
ORR	PD-L1 IC ≥1%	58.9%	42.6%	--	--	100
Grade 3/4 AEs	ITT	48.7%	42.2%	--	--	100

ITT: Intent-to-Treat; IC: Immune Cell.

The IMpassion130 trial was the first to show a clinical benefit for immunotherapy in TNBC. The differing outcomes of IMpassion130 (nab-paclitaxel) and IMpassion131 (paclitaxel) and the subsequent divergent regulatory decisions between the FDA and EMA highlight the potential impact of the chemotherapy backbone on immunotherapy efficacy in TNBC and the complexities of global drug regulation.

7. Overall Safety Profile and Management of Adverse Events

Atezolizumab, like other immune checkpoint inhibitors, has a distinct safety profile characterized by immune-mediated adverse events (irAEs), which can affect any organ system and may be severe or fatal. Understanding and managing these AEs are crucial for its safe clinical use.

Common Adverse Reactions:

• Monotherapy (≥20% incidence): Fatigue/asthenia (48%), decreased appetite (25%), nausea (24%), cough (22%), and dyspnea (22%) are frequently reported.[14]
• Combination Therapy (≥20% incidence): The profile varies depending on the combination agents but commonly includes fatigue/asthenia, nausea, alopecia, neuropathy (especially with taxanes), hematologic toxicities (anemia, neutropenia), diarrhea, constipation, decreased appetite, and rash.[13] For instance, with bevacizumab, hypertension and proteinuria are notable.[13] With cobimetinib and vemurafenib, rash, musculoskeletal pain, hepatotoxicity, pyrexia, and photosensitivity are common.[13]

Immune-Mediated Adverse Reactions (irAEs):

These are a hallmark of checkpoint inhibitor therapy and result from the enhanced immune response attacking normal tissues.2 Prompt recognition and management are essential.

• Pneumonitis: Can be fatal. Incidence is higher in patients with prior thoracic radiation. Occurred in 3% of patients on Atezolizumab monotherapy (fatal <0.1%).[13]
• Colitis: Presents with diarrhea, abdominal pain, GI bleeding. Cytomegalovirus (CMV) infection/reactivation can occur in corticosteroid-refractory cases. Occurred in 1% on monotherapy.[13]
• Hepatitis: Requires monitoring of liver function tests (AST, ALT, bilirubin). Can be severe or fatal.[2]
• Endocrinopathies:
• Adrenal insufficiency (primary or secondary).
• Hypophysitis (can present with mass effect symptoms).
• Thyroid disorders (hypothyroidism, hyperthyroidism).
• Type 1 diabetes mellitus (can present with diabetic ketoacidosis). Occurred in <0.1% (hypophysitis) to more common rates for thyroid disorders on monotherapy.[2]
• Nephritis and Renal Dysfunction: Monitor creatinine.[2]
• Dermatologic Adverse Reactions: Rash, dermatitis. Severe reactions like Stevens-Johnson syndrome (SJS), DRESS, and toxic epidermal necrolysis (TEN) can occur. One fatal TEN case reported with Tecentriq Hybreza.[2]
• Neurological Toxicities: Meningitis, encephalitis, myelitis, Guillain-Barré syndrome, myasthenic syndrome/myasthenia gravis, facial paresis.[2]
• Myocarditis/Pericarditis: Can be fatal.[16]
• Pancreatitis: Monitor amylase and lipase if suspected.[16]
• Other irAEs: Uveitis, iritis, myositis/polymyositis, rhabdomyolysis, arthritis, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.[16]

Infusion-Related/Injection Site Reactions:

• IV Infusion: Severe or life-threatening reactions can occur. Monitor for signs and symptoms. Occurred in 1.3% on monotherapy (Grade 3: 0.2%).[13]
• SC Injection (Tecentriq Hybreza): Injection site reactions occurred in 4.5% of patients.[16]

Management of irAEs:

Generally involves withholding or permanently discontinuing Atezolizumab based on severity (Grade 1-4). Systemic corticosteroid therapy (e.g., prednisone 1-2 mg/kg/day or equivalent) is often initiated, followed by a taper over at least 1 month upon improvement to Grade ≤1.13 Specific guidelines exist for different types and grades of irAEs (see Table 14).

Contraindications:

• Tecentriq (IV): Known hypersensitivity to Atezolizumab or any of its excipients.[16]
• Tecentriq Hybreza (SC): Known hypersensitivity to hyaluronidase or any of its excipients.[13]

Warnings and Precautions:

• Embryo-Fetal Toxicity: Can cause fetal harm. Pregnancy status verification and effective contraception (during and for 5 months after treatment) are required for females of reproductive potential.[13]
• Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Fatal and serious complications can occur in patients receiving allogeneic HSCT before or after PD-1/PD-L1 blockade. Patients require close monitoring.[13]
• Disease-Specific Precautions: Specific warnings apply when Atezolizumab is used in certain combinations or patient populations (e.g., risk of fatal pulmonary hemorrhage with bevacizumab combinations in NSCLC if tumor infiltrates great vessels).[16]

The mechanism of Atezolizumab, while targeting cancer by unleashing the immune system, inherently carries the risk of irAEs. This is because the disinhibition of the immune system is not confined to the tumor microenvironment but can occur systemically. The wide spectrum of potential irAEs, affecting nearly any organ, highlights that checkpoint inhibitors are not "targeted" in the sense of selectively affecting only cancer cells. Their action is a modulation of a fundamental biological process. This necessitates vigilant patient monitoring, a high index of suspicion for irAEs, and often multidisciplinary collaboration for effective diagnosis and management. The development of detailed irAE management guidelines reflects the unique challenges posed by these therapies.

Table 14: Summary of Common and Serious Immune-Mediated Adverse Reactions and General Management Principles

irAE Category	Common Symptoms/Signs	General Management Approach (Severity Dependent)	Reference(s)
Pneumonitis	New/worsening cough, dyspnea, chest pain	Withhold for Grade 2; Permanently discontinue for Grade 3 or 4. Corticosteroids.	13
Colitis/Diarrhea	Diarrhea, abdominal pain, hematochezia, mucus in stool	Withhold for Grade 2 or 3; Permanently discontinue for Grade 4. Corticosteroids. Rule out infection (e.g., CMV).	13
Hepatitis	Elevated AST/ALT/bilirubin, jaundice, fatigue, nausea	Withhold for Grade 2 (non-HCC) or Grade 3 (HCC); Permanently discontinue for Grade 3/4 (non-HCC) or Grade 4 (HCC). Corticosteroids.	2
Endocrinopathies (Hypophysitis, Thyroiditis, Adrenal Insufficiency, Type 1 DM)	Headache, visual changes, fatigue, weight changes, polyuria, polydipsia, mood changes	Withhold for Grade 2-4. Hormone replacement as needed. Corticosteroids for hypophysitis/adrenalitis. Insulin for DM.	2
Nephritis & Renal Dysfunction	Elevated creatinine, decreased urine output	Withhold for Grade 2; Permanently discontinue for Grade 3 or 4. Corticosteroids.	2
Dermatologic Reactions (incl. SJS/TEN)	Rash, pruritus, blistering, mucosal lesions	Topical/systemic corticosteroids. Withhold for Grade 3; Permanently discontinue for Grade 4 or confirmed SJS/TEN.	2
Neurological Toxicities (Meningitis, Encephalitis, Myasthenic Syndrome, GBS)	Headache, fever, confusion, seizures, muscle weakness, paresthesia	Permanently discontinue for most Grade ≥2 neurological toxicities. Corticosteroids.	2
Myocarditis/Pericarditis	Chest pain, dyspnea, arrhythmias, fatigue	Permanently discontinue for Grade ≥2. Corticosteroids.	16
Pancreatitis	Abdominal pain, nausea, vomiting, elevated amylase/lipase	Withhold for Grade ≥3 enzyme elevation or Grade 2/3 pancreatitis; Permanently discontinue for Grade 4 or recurrent. Corticosteroids.	16
Infusion-Related/ Injection Site Reactions	Fever, chills, rigors, rash, hypotension (IV); Local pain, swelling, redness (SC)	IV: Slow/interrupt infusion for Grade 1/2; Permanently discontinue for Grade 3/4. Premedication for subsequent IV doses. SC: Symptomatic treatment.	13

DM: Diabetes Mellitus; GBS: Guillain-Barré Syndrome; SJS: Stevens-Johnson Syndrome; TEN: Toxic Epidermal Necrolysis. Management typically involves withholding or discontinuing Atezolizumab and administering corticosteroids based on NCI CTCAE grade. Refer to full prescribing information for detailed grading and management.

8. Drug Interactions

The potential for drug interactions with Atezolizumab primarily concerns pharmacodynamic effects rather than pharmacokinetic ones.

Pharmacokinetic Interactions:

No formal pharmacokinetic drug interaction studies have been conducted with Atezolizumab.16 As a monoclonal antibody, Atezolizumab is cleared from circulation primarily through catabolism, similar to endogenous immunoglobulins. Therefore, metabolic drug-drug interactions mediated by cytochrome P450 enzymes or drug transporters, which are common with small molecule drugs, are not expected.16 This generally simplifies its co-administration with many other medications from a PK perspective.

Pharmacodynamic Interactions:

• Systemic Corticosteroids and Immunosuppressants: The use of systemic corticosteroids or other immunosuppressants before initiating Atezolizumab therapy should generally be avoided. This is due to their potential to interfere with the pharmacodynamic activity and efficacy of Atezolizumab, which relies on enhancing an immune response.[16] However, systemic corticosteroids or other immunosuppressants can be used to treat immune-mediated adverse reactions that arise after starting Atezolizumab treatment.[16] This distinction is crucial for managing irAEs without unnecessarily compromising the intended therapeutic effect of Atezolizumab.
• Other Medicines: While one general source suggests no known interactions [109], it is always prudent for healthcare providers to be aware of all concomitant medications, including prescription drugs, over-the-counter products, vitamins, and herbal supplements, to assess any potential for unforeseen interactions.

Administration Considerations:

• Atezolizumab should not be mixed with other medicinal products in the same infusion bag or syringe.[108]
• It should not be co-administered with other drugs through the same intravenous line.[108]
• When Atezolizumab is given in combination regimens on the same day as other agents (e.g., bevacizumab or chemotherapy), Atezolizumab should generally be administered prior to the other drugs.[108]

The primary concern for drug interactions with Atezolizumab is the potential for pharmacodynamic antagonism if systemic immunosuppressants are used prior to or concurrently (for reasons other than irAE management) with Atezolizumab therapy. The lack of significant metabolic drug-drug interactions is a favorable characteristic for a drug often used in complex, multi-agent cancer treatment regimens.

9. Ongoing Research and Future Perspectives

The clinical development of Atezolizumab is ongoing, with research focusing on expanding its utility into new indications, exploring novel combination therapies, identifying better predictive biomarkers, and understanding mechanisms of resistance.

New Indications and Combinations:

• Head and Neck Cancer: The Phase III IMvoke010 trial evaluated maintenance Atezolizumab in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) following multimodal definitive treatment. As of March 2025, results indicated that the trial did not meet its primary endpoint of event-free survival (EFS) or overall survival (OS) compared with placebo.[110]
• Hepatocellular Carcinoma (HCC): The FAB-HCC Phase II pilot study (NCT05750030; EudraCT 2022-000234-42), registered in January 2023, is assessing the safety and efficacy of Fecal Microbiota Transplant (FMT) combined with Atezolizumab/bevacizumab in patients with HCC who failed to achieve or maintain an objective response to Atezolizumab/bevacizumab alone. This trial explores modulating the gut microbiome as a strategy to potentially overcome immunotherapy resistance.[111]
• Non-Small Cell Lung Cancer (NSCLC): An update on the Phase II/III SKYSCRAPER-06 study in metastatic non-squamous NSCLC was provided in July 2024.[33] Further details on this study's progress are anticipated.
• Small Cell Lung Cancer (SCLC): A clinical study of Reqorsa Immunogene Therapy in combination with Tecentriq is underway, with the first patient dosed in May 2024. This combination received FDA Fast Track Designation in June 2023, indicating its potential to address unmet needs in SCLC.[33]

Biomarkers and Resistance Mechanisms:

A significant area of research is the identification of more robust predictive biomarkers beyond PD-L1 expression to better stratify patients and optimize treatment selection.34 Understanding and overcoming both primary (innate) and acquired resistance to PD-L1/PD-1 blockade remains a major challenge in immuno-oncology.4 The exploration of FMT in the FAB-HCC trial 111 is indicative of the growing interest in the gut microbiome's role in influencing immunotherapy outcomes and potentially reversing resistance.

Formulation Development:

The approval of Tecentriq Hybreza, the subcutaneous formulation of Atezolizumab co-formulated with hyaluronidase, represents an important advancement aimed at improving patient convenience and potentially optimizing healthcare resource utilization by significantly reducing administration time compared to the intravenous formulation.11

Current research endeavors with Atezolizumab, such as the investigation of FMT in HCC and combinations with novel agents like Reqorsa in SCLC, reflect key strategic directions in oncology. These efforts are focused on tackling the pervasive issue of immunotherapy resistance and exploring innovative synergistic combinations. While checkpoint inhibitors have transformed cancer treatment, a substantial proportion of patients either do not respond initially or develop resistance over time. Strategies like modulating the gut microbiome are emerging as a means to enhance immunotherapy efficacy, suggesting that factors beyond the tumor and its immediate microenvironment play crucial roles in determining treatment outcomes. The continuous exploration of new combination partners aims to target diverse resistance pathways or further potentiate the desired immune response. Conversely, the outcome of trials like IMvoke010 in head and neck cancer, where Atezolizumab did not demonstrate significant benefit as maintenance therapy [110], underscores that success in one tumor type or therapeutic setting does not automatically translate to others. This highlights the critical need for indication-specific research and a tailored approach to drug development in the complex field of immuno-oncology.

10. Conclusion and Detailed Recommendations

Atezolizumab (Tecentriq®/Tecentriq Hybreza™) has firmly established itself as a significant therapeutic agent in the oncology armamentarium. As a humanized monoclonal antibody targeting PD-L1, it has demonstrated clinically meaningful efficacy in a variety of malignancies, including non-small cell lung cancer (NSCLC) across different stages and settings, extensive-stage small cell lung cancer (SCLC), unresectable hepatocellular carcinoma (HCC), BRAF V600 mutation-positive melanoma, and alveolar soft part sarcoma (ASPS). Its utility extends from monotherapy in biomarker-selected populations to combination regimens with chemotherapy, targeted agents, and other immunotherapies.

Key Strengths:

The primary strength of Atezolizumab lies in its ability to elicit durable anti-tumor responses and improve survival outcomes in several cancer types that were historically challenging to treat. For many patients, its safety profile is manageable, particularly when compared to traditional cytotoxic chemotherapy. The recent introduction of the subcutaneous formulation, Tecentriq Hybreza, offers a significant improvement in patient convenience and flexibility in treatment administration.

Key Limitations and Challenges:

Despite its successes, Atezolizumab therapy is not without limitations. A significant proportion of patients do not respond to treatment (primary resistance), and others who initially respond may later develop acquired resistance. PD-L1 expression, while utilized as a predictive biomarker for some indications, has inherent limitations in accurately identifying all patients who may benefit, and its assessment methodologies can be complex. Furthermore, the unique spectrum of immune-mediated adverse events (irAEs) associated with Atezolizumab requires vigilant monitoring and specialized management, which can sometimes be life-threatening. The withdrawal of certain accelerated approvals by the FDA, notably for specific urothelial carcinoma and triple-negative breast cancer indications, due to the failure of confirmatory trials to substantiate initial findings, underscores the ongoing need for robust evidence generation.

Clinical Practice Recommendations:

Based on the synthesized data, the following recommendations are pertinent for the clinical use of Atezolizumab:

1. Adherence to Approved Indications: Clinicians must strictly adhere to the specific FDA and EMA approved indications, including patient selection criteria based on cancer type, stage, line of therapy, PD-L1 status (where applicable), and relevant genetic markers (e.g., EGFR/ALK, BRAF).
2. Biomarker Testing: Perform validated PD-L1 testing as per regulatory requirements for indications where it is mandated for patient selection. Understand the nuances of different assays and scoring systems (TC vs. IC).
3. Management of Immune-Mediated Adverse Events: Healthcare providers must be thoroughly familiar with the spectrum of potential irAEs. Early recognition, accurate diagnosis, and prompt implementation of established management guidelines (typically involving corticosteroids and temporary or permanent discontinuation of Atezolizumab based on severity) are critical to minimize morbidity. Multidisciplinary consultation is often beneficial.
4. Combination Therapy Considerations: When using Atezolizumab in combination regimens, clinicians must be aware of the additive or overlapping toxicity profiles of all agents involved and manage patients accordingly.
5. Patient Education: Comprehensive patient education regarding the mechanism of action, potential benefits, common and serious side effects (especially irAEs), and the importance of promptly reporting any new or worsening symptoms is essential for shared decision-making and optimal safety.

Future Research Directions:

The field of immuno-oncology is rapidly evolving, and future research involving Atezolizumab should focus on:

1. Novel Combination Strategies: Continued investigation into rational combinations with other immunotherapies, targeted agents, chemotherapy, radiotherapy, and novel modalities (e.g., microbiome modulators, oncolytic viruses) to improve response rates, deepen responses, and overcome resistance.
2. Biomarker Refinement: Development and validation of more precise predictive biomarkers beyond PD-L1, potentially including composite biomarker signatures (e.g., tumor mutational burden, gene expression profiles, microbiome characteristics), to better identify patients most likely to benefit or those at higher risk of toxicity.
3. Understanding Resistance Mechanisms: Elucidating the molecular and cellular mechanisms underlying primary and acquired resistance to Atezolizumab to develop effective strategies to prevent or reverse it.
4. Long-Term Outcomes and Sequencing: Further research into the long-term survival and quality of life outcomes for patients treated with Atezolizumab, and optimal sequencing strategies with other available therapies.
5. Expansion to New Settings: Exploration of Atezolizumab's efficacy in other tumor types and in earlier stages of disease, such as neoadjuvant settings.

Overall Impact:

Atezolizumab has undeniably transformed the treatment landscape for several cancers, offering new therapeutic avenues and improved prognoses for many patients. Its journey, marked by significant approvals and necessary regulatory adjustments, reflects the dynamic process of drug development in oncology. The balance between fostering rapid innovation through mechanisms like accelerated approval and ensuring confirmed, robust clinical benefit through rigorous post-marketing evaluation is paramount. Atezolizumab's story is a compelling case study in this ongoing endeavor, highlighting the continuous cycle of innovation, evidence generation, and refinement that characterizes the modern pursuit of more effective cancer therapies. Continued research and clinical experience will further delineate its optimal role in cancer care.

Works cited

1. Definition of atezolizumab - NCI Drug Dictionary - NCI, accessed May 23, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/atezolizumab
2. Atezolizumab - StatPearls - NCBI Bookshelf, accessed May 23, 2025, https://www.ncbi.nlm.nih.gov/books/NBK567758/
3. Product review on the Anti-PD-L1 antibody atezolizumab - PMC - PubMed Central, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5806639/
4. Atezolizumab - Wikipedia, accessed May 23, 2025, https://en.wikipedia.org/wiki/Atezolizumab
5. Atezolizumab Monograph for Professionals - Drugs.com, accessed May 23, 2025, https://www.drugs.com/monograph/atezolizumab.html
6. Tecentriq (atezolizumab) - Roche, accessed May 23, 2025, https://www.roche.com/solutions/pharma/productid-8c738504-101a-40b9-867b-d907c578df51
7. What is TECENTRIQ?, accessed May 23, 2025, https://tecentriq.global/home/what-is-tecentriq.html
8. Atezolizumab | Genentech Prescribing & Product Information, accessed May 23, 2025, https://www.genentech-medinfo.com/our-products/oncology/tecentriq.html
9. Atezolizumab: Uses, Interactions, Mechanism of Action | DrugBank ..., accessed May 23, 2025, https://go.drugbank.com/drugs/DB11595
10. Atezolizumab - brand name list from Drugs.com, accessed May 23, 2025, https://www.drugs.com/ingredient/atezolizumab.html
11. FDA Approves Subcutaneous Atezolizumab and Hyaluronidase-tqjs for Use in All Indications of IV Atezolizumab - OncLive, accessed May 23, 2025, https://www.onclive.com/view/fda-approves-subcutaneous-atezolizumab-and-hyaluronidase-tqjs-for-use-in-all-indications-of-iv-atezolizumab
12. Home Page | TECENTRIQ HYBREZA™ (atezolizumab and hyaluronidase-tqjs), accessed May 23, 2025, https://www.tecentriq-hcp.com/hybreza.html
13. www.accessdata.fda.gov, accessed May 23, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761347s000lbl.pdf
14. Tecentriq® (atezolizumab) - Information for Healthcare Providers - Genentech, accessed May 23, 2025, https://www.gene.com/medical-professionals/medicines/tecentriq
15. FDA Approval Summary: Atezolizumab as Adjuvant Treatment Following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC - PMC, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10440223/
16. www.ema.europa.eu, accessed May 23, 2025, https://www.ema.europa.eu/en/documents/product-information/tecentriq-epar-product-information_en.pdf
17. 05052021_MR_IMpower110 EMA approval _en - Roche, accessed May 23, 2025, https://assets.roche.com/imported/01_05052021_MR_IMpower110_EMA_Approval__En.pdf
18. TECENTRIQ® (atezolizumab) HCP | Efficacy, Safety, PI & MOA, accessed May 23, 2025, https://www.tecentriq-hcp.com/
19. Atezolizumab - SEER*Rx Interactive Antineoplastic Drugs Database, accessed May 23, 2025, https://seer.cancer.gov/seertools/seerrx/rx/551ac632e4b0bc5c16bdb401/
20. atezolizumab (TECENTRIQ - Coverage Policy Manual - Arkansas Blue Cross and Blue Shield, accessed May 23, 2025, https://secure.arkansasbluecross.com/members/report.aspx?policyNumber=2016016&viewIntro=yes
21. Tecentriq - This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed May 23, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761034s043lbl.pdf
22. Tecentriq | European Medicines Agency (EMA), accessed May 23, 2025, https://www.ema.europa.eu/en/medicines/human/EPAR/tecentriq
23. Adjuvant Atezolizumab Approved in Europe for High-Risk NSCLC With PD-L1 of ≥50%, accessed May 23, 2025, https://www.onclive.com/view/adjuvant-atezolizumab-approved-in-europe-for-high-risk-nsclc-with-pd-l1-of-50-
24. European Commission approves Roche's Tecentriq in combination with chemotherapy for the initial treatment of people with extensive-stage small cell lung cancer, accessed May 23, 2025, https://www.roche.com/media/releases/med-cor-2019-09-06b
25. Atezolizumab Combo Approved in Europe for Small Cell Lung Cancer - OncLive, accessed May 23, 2025, https://www.onclive.com/view/atezolizumab-combo-approved-in-europe-for-small-cell-lung-cancer
26. European Commission approves Roche's Tecentriq in combination with Avastin for the treatment of people with the most common form of liver cancer, accessed May 23, 2025, https://www.roche.com/media/releases/med-cor-2020-11-02
27. 20190829_MR_EC approval IMpassion130, accessed May 23, 2025, https://ml-eu.globenewswire.com/Resource/Download/85ab8434-39c0-4d10-bf30-6937546a8abc
28. Roche's Tecentriq in combination with chemotherapy (including Abraxane) meets primary endpoint of improved pathological complete response, regardless of PD-L1 status, as initial treatment for people with early triple-negative breast cancer, accessed May 23, 2025, https://www.roche.com/media/releases/med-cor-2020-06-18
29. CHMP recommends EU approval of Roche's Tecentriq as adjuvant treatment for a subset of people with early-stage non-small cell lung cancer, accessed May 23, 2025, https://www.roche.com/investors/updates/inv-update-2022-04-22b
30. Lung Cancer - tecentriq, accessed May 23, 2025, https://tecentriq.global/home/indication/lung-cancer.html
31. Atezolizumab (Tecentriq®) as monotherapy for the first-line treatment of advanced NSCLC, accessed May 23, 2025, https://eprints.aihta.at/1543/1/Fact%20Sheet%20Nr.190.pdf
32. Solid Tumors Withdrawn Phase 2 Trials for Atezolizumab (DB11595) | DrugBank Online, accessed May 23, 2025, https://go.drugbank.com/indications/DBCOND0029860/clinical_trials/DB11595?phase=2&status=withdrawn
33. Tecentriq (atezolizumab) FDA Approval History - Drugs.com, accessed May 23, 2025, https://www.drugs.com/history/tecentriq.html
34. Atezolizumab in advanced non-small cell lung cancer - PMC, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5723868/
35. PD-L1 (Atezolizumab) Recombinant Human Monoclonal Antibody (RG7446), Functional Grade - Thermo Fisher Scientific, accessed May 23, 2025, https://www.thermofisher.com/antibody/product/PD-L1-Atezolizumab-Antibody-clone-RG7446-Recombinant-Monoclonal/LT1750-100MG
36. Atezolizumab TNBC Indication Withdrawn By Manufacturer After Talks With FDA, accessed May 23, 2025, https://www.cancernetwork.com/view/atezolizumab-tnbc-indication-withdrawn-by-manufacturer-after-talks-with-fda
37. Update on U.S. Indication for Atezolizumab in PD-L1–Positive Metastatic Triple-Negative Breast Cancer - The ASCO Post, accessed May 23, 2025, https://ascopost.com/issues/september-25-2021/update-on-us-indication-for-atezolizumab-in-pd-l1-positive-metastatic-triple-negative-breast-cancer/
38. Annotation of EMA Label for atezolizumab and ALK, CD274, EGFR - PharmGKB, accessed May 23, 2025, https://www.pharmgkb.org/labelAnnotation/PA166182926
39. Atezolizumab (Tecentriq®): RMP summary - Swissmedic, accessed May 23, 2025, https://www.swissmedic.ch/dam/swissmedic/de/dokumente/marktueberwachung/rmp/atezolizumab_tecentriq-rmp-summary.pdf.download.pdf/Atezolizumab_Tecentriq_RMP_Summary.pdf
40. ESMO-MCBS Scorecards - Atezolizumab, accessed May 23, 2025, https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-235-1
41. Updated OS Analysis Favors Frontline Atezolizumab in PD-L1–High NSCLC - OncLive, accessed May 23, 2025, https://www.onclive.com/view/updated-os-analysis-favors-frontline-atezolizumab-in-pd-l1-high-nsclc
42. Adjuvant Atezolizumab Improves DFS While Delaying Relapse in NSCLC Subgroups, accessed May 23, 2025, https://www.targetedonc.com/view/adjuvant-atezolizumab-improves-dfs-while-delaying-relapse-in-nsclc-subgroups
43. Oncology Advances: Adjuvant Atezolizumab Improves Survival Outcomes for Non-Small Cell Lung Cancer Regardless of Disease Stage, Regional Lymph Node Status, accessed May 23, 2025, https://www.hmpgloballearningnetwork.com/site/onc/advances/adjuvant-atezolizumab-improves-survival-outcomes-non-small-cell-lung-cancer
44. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial - PubMed, accessed May 23, 2025, https://pubmed.ncbi.nlm.nih.gov/31122901/
45. Frontline Atezolizumab Plus Carboplatin/Nab-Paclitaxel Improves OS in Nonsquamous NSCLC - OncLive, accessed May 23, 2025, https://www.onclive.com/view/frontline-atezolizumab-plus-carboplatinnabpaclitaxel-improves-os-in-nonsquamous-nsclc
46. TECENTRIQ® (atezolizumab) injection, for intravenous use - accessdata.fda.gov, accessed May 23, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761034s053lbl.pdf
47. Cancer Immunotherapy Treatment for NSCLC, ES-SCLC, HCC, & Advanced Melanoma | TECENTRIQ® (atezolizumab), accessed May 23, 2025, https://www.tecentriq.com/
48. Population Pharmacokinetics and Exposure‐Response of Subcutaneous Atezolizumab in Patients With Non‐Small Cell Lung Cancer - PubMed Central, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12001254/
49. FDA approves atezolizumab with chemotherapy and bevacizumab for first-line treatment of metastatic non-squamous NSCLC, accessed May 23, 2025, https://www.fda.gov/drugs/fda-approves-atezolizumab-chemotherapy-and-bevacizumab-first-line-treatment-metastatic-non-squamous
50. Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) FDA Approval History, accessed May 23, 2025, https://www.drugs.com/history/tecentriq-hybreza.html
51. Atezolizumab (TECENTRIQ) - FDA, accessed May 23, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/atezolizumab-tecentriq
52. FDA approves new, targeted treatment for bladder cancer, accessed May 23, 2025, https://www.fda.gov/news-events/press-announcements/fda-approves-new-targeted-treatment-bladder-cancer
53. FDA Grants Genentech's Tecentriq (Atezolizumab) Accelerated Approval as Initial Treatment for Certain People with Advanced Bladder Cancer, accessed May 23, 2025, https://www.gene.com/media/press-releases/14660/2017-04-17/fda-grants-genentechs-tecentriq-atezoliz
54. FDA approves atezolizumab for BRAF V600 unresectable or metastatic melanoma, accessed May 23, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-braf-v600-unresectable-or-metastatic-melanoma
55. FDA Approves Genentech's Tecentriq plus Cotellic and Zelboraf for People With Advanced Melanoma, accessed May 23, 2025, https://www.gene.com/media/press-releases/14868/2020-07-30/fda-approves-genentechs-tecentriq-plus-c
56. FDA grants approval to atezolizumab for alveolar soft part sarcoma, accessed May 23, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-approval-atezolizumab-alveolar-soft-part-sarcoma
57. NCI clinical trial leads to atezolizumab approval for advanced alveolar soft part sarcoma, accessed May 23, 2025, https://www.cancer.gov/news-events/press-releases/2022/nci-trial-atezolizumab-approval-alveolar-soft-part-sarcoma
58. Genentech Withdraws Atezolizumab Indication for Certain Patients with Metastatic Bladder Cancer - Targeted Oncology, accessed May 23, 2025, https://www.targetedonc.com/view/genentech-withdraws-atezolizumab-indication-for-certain-patients-with-metastatic-bladder-cancer
59. Atezolizumab FDA indication for pretreated bladder cancer voluntarily withdrawn, accessed May 23, 2025, https://www.urologytimes.com/view/atezolizumab-fda-indication-for-pretreated-bladder-cancer-voluntarily-withdrawn
60. Roche Withdraws Atezolizumab Prior-Platinum Treated Metastatic Bladder Cancer Indication in the United States - OncLive, accessed May 23, 2025, https://www.onclive.com/view/roche-withdraws-atezolizumab-prior-platinum-treated-metastatic-bladder-cancer-indication-in-the-united-states
61. Atezolizumab - ESMO-MCBS Scorecards | ESMO, accessed May 23, 2025, https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-171-1
62. Atezolizumab No Longer Available in US for a Certain Type of Bladder Cancer, accessed May 23, 2025, https://www.cancernetwork.com/view/atezolizumab-no-longer-available-in-us-for-a-certain-type-of-bladder-cancer
63. Genentech Provides Update on Tecentriq U.S. Indication for Previously Untreated Metastatic Bladder Cancer, accessed May 23, 2025, https://www.gene.com/media/statements/ps_112822
64. Human medicines European public assessment report (EPAR): Tecentriq, atezolizumab, Date of authorisation: 20/09/2017, Revision: 31, Status, accessed May 23, 2025, https://efim.org/node/141092
65. The European Medicines Agency review of the initial application of atezolizumab and the role of PD-L1 expression as biomarker for checkpoint inhibitors, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7910722/
66. Tecentriq-Avastin Combo Approved in Europe for Advanced or Inoperable Liver Cancer, accessed May 23, 2025, https://immuno-oncologynews.com/2020/11/06/tecentriq-avastin-combo-approved-europe-to-treat-advanced-or-inoperable-liver-cancer/
67. Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients With Lung Cancer [IMpower010] - LarvolClin, accessed May 23, 2025, https://clin.larvol.com/trial-detail/NCT02486718
68. Adjuvant Atezolizumab Sustains Survival Vs BSC in Stage IB to IIIA NSCLC, accessed May 23, 2025, https://www.cancernetwork.com/view/adjuvant-atezolizumab-sustains-survival-vs-bsc-in-stage-ib-to-iiia-nsclc
69. IMpower010: Characterisation of Patients With Stage II-IIIA PD-L1 Tumour Cell ≥50% NSCLC Who Were Disease - Medically, accessed May 23, 2025, https://medically.gene.com/content/dam/pdmahub/restricted/oncology/esmo-2024/ESMO-2024-poster-felip-IMpower010-characterisation-of-patients.pdf?specialtyTag=pdmahub:speciality/ophthalmology&actionid=share-feedback&about=A%20Unified%20Deep%20Learning%20Approach%20for%20OCT%20Segmentation%20From%20Different%20Devices%20and%20Retinal%20Diseases&actionid=share-feedback&about=A%20Unified%20Deep%20Learning%20Approach%20for%20OCT%20Segmentation%20From%20Different%20Devices%20and%20Retinal%20Diseases
70. IMpower010: Exploratory analysis of disease-free survival by KRAS status in patients with stage II-IIIA NSCLC treated with adjuvant atezolizumab vs best supportive care. - ASCO Publications, accessed May 23, 2025, https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8522
71. IMpower110 Clinical Trial Results | TECENTRIQ® (atezolizumab), accessed May 23, 2025, https://www.tecentriq-hcp.com/metastatic-nsclc/efficacy/impower110-clinical-trial-results.html
72. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC, accessed May 23, 2025, https://www.researchgate.net/publication/345437474_Atezolizumab_for_First-Line_Treatment_of_PD-L1-Selected_Patients_with_NSCLC
73. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC - Roche, accessed May 23, 2025, https://image.email-epicx.roche.com/lib/fe2f11737364047c7d1174/m/1/3f5036e5-6991-4f68-8aeb-15cc88d617e1.pdf
74. A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) - Cancer Trial Results, accessed May 23, 2025, https://clin.larvol.com/trial-detail/NCT02366143
75. ESMO-MCBS Scorecards - Atezolizumab, accessed May 23, 2025, https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-155-1
76. ASCO 2018: First-Line Atezolizumab Improves Survival in Advanced NSCLC, accessed May 23, 2025, https://www.esmo.org/oncology-news/archive/asco-2018-first-line-atezolizumab-improves-survival-in-advanced-nsclc
77. Atezolizumab Versus Docetaxel in Pretreated Patients With NSCLC ..., accessed May 23, 2025, https://pubmed.ncbi.nlm.nih.gov/33166718/
78. Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer, accessed May 23, 2025, https://jitc.bmj.com/content/10/11/e005581
79. Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy - Frontiers, accessed May 23, 2025, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1306311/full
80. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study - ASCO Publications, accessed May 23, 2025, https://ascopubs.org/doi/10.1200/JCO.22.02823
81. Atezolizumab - ESMO-MCBS Scorecards, accessed May 23, 2025, https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-194-1
82. IMpower133 efficacy results in 1L ES-SCLC | TECENTRIQ® (atezolizumab), accessed May 23, 2025, https://www.tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html
83. Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial - ResearchGate, accessed May 23, 2025, https://www.researchgate.net/publication/378340437_Atezolizumab_Plus_Carboplatin_and_Etoposide_in_Patients_with_Untreated_Extensive-Stage_Small-Cell_Lung_Cancer_Interim_Results_of_the_MAURIS_Phase_IIIb_Trial
84. Five-year survival in patients with ES-SCLC treated with atezolizumab in IMpower133: IMbrella A extension study results - Medically, accessed May 23, 2025, https://medically.gene.com/global/en/unrestricted/oncology/WCLC-2023/wclc-2023-presentation-liu-five-year-survival-in-patien.html?cid=slpsaan20242404xx
85. IMpower133 Update Atezolizumab Plus Carboplatin/Etoposide for Extensive-Stage Small Cell Lung Cancer - The ASCO Post, accessed May 23, 2025, https://ascopost.com/news/january-2021/impower133-update-atezolizumab-plus-carboplatinetoposide-for-extensive-stage-small-cell-lung-cancer/
86. IMbrave150: Exploratory analysis to examine the association between bevacizumab (bev) ever being skipped and bev never being skipped in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bev in a global phase 3 study. - ResearchGate, accessed May 23, 2025, https://www.researchgate.net/publication/367767540_IMbrave150_Exploratory_analysis_to_examine_the_association_between_bevacizumab_bev_ever_being_skipped_and_bev_never_being_skipped_in_patients_with_unresectable_hepatocellular_carcinoma_HCC_treated_wit
87. Updates on Systemic Therapy for Hepatocellular Carcinoma - ASCO Publications, accessed May 23, 2025, https://ascopubs.org/doi/10.1200/EDBK_430028
88. IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). | Journal of Clinical Oncology - ASCO Publications, accessed May 23, 2025, https://ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.267
89. Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150 - PMC, accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11649257/
90. Atezolizumab Combined with Bevacizumab in Unresectable HCC - ESMO, accessed May 23, 2025, https://www.esmo.org/oncology-news/atezolizumab-combined-with-bevacizumab-in-unresectable-hcc
91. A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma - Cancer Trial Results, accessed May 23, 2025, https://clin.larvol.com/trial-detail/NCT03434379
92. Study Explores the Addition of First-Line Atezolizumab in BRAF V600–Mutant Advanced Melanoma - The ASCO Post, accessed May 23, 2025, https://ascopost.com/issues/january-25-2023/study-explores-the-addition-of-first-line-atezolizumab-in-braf-v600-mutant-advanced-melanoma/
93. Overall survival with first-line atezolizumab in combination with ..., accessed May 23, 2025, https://pubmed.ncbi.nlm.nih.gov/36460017/
94. Phase II study of atezolizumab in advanced alveolar soft part sarcoma (ASPS)., accessed May 23, 2025, https://scholars.duke.edu/display/pub1503015
95. Atezolizumab for advanced alveolar soft part sarcoma - Digital Commons@Becker, accessed May 23, 2025, https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=4513&context=oa_4
96. Atezolizumab Shrinks Alveolar Soft Part Sarcomas - NCI, accessed May 23, 2025, https://www.cancer.gov/news-events/cancer-currents-blog/2023/atezolizumab-effective-alveolar-soft-part-sarcoma
97. ECC 2015: Atezolizumab in Locally Advanced or Metastatic Urothelial Carcinoma: Results of the IMvigor 210 Study - The ASCO Post, accessed May 23, 2025, https://ascopost.com/News/33901
98. Atezolizumab monotherapy for metastatic urothelial carcinoma: final ..., accessed May 23, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11667038/
99. A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130) - LarvolClin, accessed May 23, 2025, https://clin.larvol.com/trial-detail/NCT02425891
100. Addition of Atezolizumab to Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: IMpassion130 Trial - The ASCO Post, accessed May 23, 2025, http://ascopost.com/issues/january-25-2019/addition-of-atezolizumab-to-nab-paclitaxel-in-advanced-triple-negative-breast-cancer/
101. Abstract PD14-05: Genomic profiling and clinical outcomes with first-line atezolizumab and nab-paclitaxel in triple-negative breast cancer: An exploratory analysis from the phase 3 IMpassion130 trial, accessed May 23, 2025, https://aacrjournals.org/cancerres/article/81/4_Supplement/PD14-05/647943/Abstract-PD14-05-Genomic-profiling-and-clinical
102. 37OSubgroup analysis of IMpassion130: Atezolizumab + nab-paclitaxel (nab-P) in patients (pts) with advanced triple-negative breast cancer (TNBC) in Asian countries | Request PDF - ResearchGate, accessed May 23, 2025, https://www.researchgate.net/publication/337475583_37OSubgroup_analysis_of_IMpassion130_Atezolizumab_nab-paclitaxel_nab-P_in_patients_pts_with_advanced_triple-negative_breast_cancer_TNBC_in_Asian_countries
103. breast cancer, metastatic - Christie Repository, accessed May 23, 2025, https://christie.openrepository.com/bitstream/handle/10541/623524/Primary.pdf?sequence=1&isAllowed=y
104. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer - Sci-Hub, accessed May 23, 2025, https://www.sci-hub.se/downloads/2019-01-28//a4/schmid2018.pdf
105. Dosing & Administration | TECENTRIQ HYBREZA™ (atezolizumab and hyaluronidase-tqjs), accessed May 23, 2025, https://www.tecentriq-hcp.com/hybreza/dosing-and-administration/dosing.html
106. TECENTRIQ® (atezolizumab) offers 3 flexible dosing options, accessed May 23, 2025, https://www.tecentriq-hcp.com/sclc/dosing-and-administration/dosing.html
107. Atezolizumab (Tecentriq) Drug Information - Understanding Cancer Immunotherapy Research, accessed May 23, 2025, https://www.ucir.org/immunotherapy-drugs/atezolizumab
108. atezolizumab - Cancer Care Ontario, accessed May 23, 2025, https://www.cancercareontario.ca/en/system/files_force/atezolizumab.pdf?download=1
109. www.webmd.com, accessed May 23, 2025, https://www.webmd.com/drugs/2/drug-171808/atezolizumab-intravenous/details#:~:text=There%20are%20no%20known%20interactions%20between%20Tecentriq%20and%20other%20medicines,other%20supplements%20you%20are%20using.
110. Tecentriq Falls Short of Primary Endpoint in IMvoke010 Trial for Locally Advanced Head and Neck Cancer, accessed May 23, 2025, https://www.appliedclinicaltrialsonline.com/view/tecentriq-imvoke010-trial-head-neck-cancer
111. (PDF) Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab – the FAB-HCC pilot study - ResearchGate, accessed May 23, 2025, https://www.researchgate.net/publication/390805392_Study_protocol_Fecal_Microbiota_Transplant_combined_with_AtezolizumabBevacizumab_in_Patients_with_Hepatocellular_Carcinoma_who_failed_to_achieve_or_maintain_objective_response_to_AtezolizumabBevacizum