REAL-WORLD DURVALUMAB IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER

Recruiting

• Conditions: Small Cell Lung Carcinoma

• Registration Number: NCT06826677
• Lead Sponsor: AstraZeneca

Brief Summary

Primary lung cancer is one of the most common malignancies and causes of cancer-related death worldwide \[Passiglia et al., 2019; Bade and Dela Cruz, 2020\].

Lung cancer is classified into different types, among which small cell lung cancer (SCLC), accounting for 13%-20% of all lung cancer cases \[Pezzuto et al., 2019; Torres-Durán et al., 2021\], is an aggressive form of neuroendocrine malignancy characterized by rapid growth, tendency to disseminate early and high relapse rates \[El Sayed and Blais, 2021\].

There are persistently limited treatment options for SCLC \[DiBonaventura et al., 2019; El Sayed and Blais, 2021\], and the current clinical approach to SCLC treatment is chosen irrespective of biological subtype \[Rudin et al., 2021; Keogh et al., 2022\]. First-line treatments for ES-SCLC have been platinum-based chemotherapy combinations for decades, without significant differences in Overall Survival (OS) between cisplatin and carboplatin, valuing flexibility in the choice of platinum agent in treatment decision making for individual patients \[Dingemans et al., 2021\]. However, despite the high initial response rate, the prognosis remains poor \[Zhang et al., 2021; Johal et al., 2021\].

In recent years, immunotherapy has dramatically modified cancer treatment across several malignancies and has been an active area of investigation in SCLC \[Calles et al., 2019; Dingemans et al., 2021\]. Treatments that combine chemotherapy and immune checkpoint inhibitors (ICIs), such as durvalumab and atezolizumab, can increase immune responses to tumor cells, resulting in improved efficacy in ES-SCLC compared to chemotherapy alone \[Esposito et al., 2020; Konala et al., 2020; Hiddinga et al., 2021; Lim and Kang, 2021\]. These treatment regimens have been approved in many countries \[Wang et al., 2022\] and are now the standard of care in the ES-SCLC first-line setting, according to the ESMO \[Dingemans et al., 2021\] and the NCCN Clinical Practice Guidelines in Oncology \[Ganti et al., 2022\].

Durvalumab is a fully human, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that selectively blocks the interaction of programmed cell death ligand-1 (PD-L1) with PD-1 and CD80 \[IMFINZI® (durvalumab) Summary of Product Characteristics\]. The phase III CASPIAN study (ClinicalTrials.gov identifier: NCT03043872) showed that the addition of durvalumab to a combination regimen of etoposide with either cisplatin or carboplatin significantly improved OS compared with etoposide and platinum alone, with a manageable tolerability profile \[Paz-Ares et al., 2019; Goldman et al., 2021; Paz-Ares et al., 2022\].

Following the CASPIAN study, an Early Access Programme (EAP) to provide pre-approval access to durvalumab plus platinum-etoposide for ES-SCLC patients eligible to receive first-line platinum-based chemotherapy (D419QR00007 EAP, hereafter called 'CASPIAN EAP') was activated in Italy in March 2020, including 125 subjects across 39 oncology centers.

Clinical trials have demonstrated significant efficacy and a favorable safety profile of durvalumab combined with chemotherapy in ES-SCLC \[Paz-Ares et al., 2022\]. On the other hand, it is estimated that stringent eligibility criteria may exclude up to 70% of patients with lung cancer from ICI clinical trials \[von Itzstein et al., 2020\]. Understanding the efficacy and safety of ICIs in a more heterogeneous patient population than in randomized controlled trials is critical to realizing the full potential of these therapies. To fill the gap between strictly controlled clinical trial populations and actual lung cancer patients managed in clinical practice, observational studies from real-world settings are emerging \[von Itzstein et al., 2020\]. Although real-world studies are unable to achieve the high internal validity of randomized controlled trials (RCTs), accurately performed analyses of real-world data can provide valuable complementary results \[Nazha et al., 2021\].

In conclusion, considering that ES-SCLC are often elderly patients with multiple comorbidities \[Schulkes et al., 2016\] for whom the treatment decision-making is challenging \[DiBonaventura et al., 2019\], the ARAL observational study will contribute to filling the information gap by collecting real-world data from the CASPIAN EAP to better describe durvalumab treatment outcomes and treatment patterns among patients diagnosed with ES-SCLC in Italy.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-30
• Study First Submitted: 2025-02-10
• Study First Submitted QC: 2025-02-10
• Study First Posted: 2025-02-14
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-14
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Patients with diagnosis of extensive-stage Small Cell Lung Cancer (ES-SCLC).
2. Patients entered, at least 24 months prior to the study inclusion, the D419QR00007 Early Access Programme (CASPIAN EAP) implemented in Italy.
3. Adult patients (aged ≥ 18 years) at the time of inclusion in the CASPIAN EAP.
4. Patients having performed at least one administration of durvalumab treatment in the CASPIAN EAP.
5. Patients (or their legally acceptable representatives) who have signed the subject informed consent and privacy form, if applicable.

Exclusion Criteria

1. Patients with unavailable medical chart.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall survival	From index date to death or date of enrollment in the study (up to 5 years)	Median OS
Overall Survival	From index date to death or date of enrollment in the study (up to 5 years)	Mean OS

Secondary Outcome Measures

Name	Time	Method
Overall Survival	24 months after index date	OS rate at 24 months after index date (defined as platinum-etoposide chemotherapy C1 D1).
Progression Free Survival	12, 18, 24 months after index date	PFS rate at 12, 18 and 24 months after index date.
Progression free survival	From index date to death or progression or date of enrollment in the study (up to 5 years)	Median PFS
Time to discontinuation	From index date to last dose of treatment with durvalumab or death or date of enrollment in the study (up to 5 years)	Median TTD
Time to First Subsequent Therapy or Death	From index date to start of other cancer treatment or death or date of enrollment in the study (up to 5 years)	Median TFST
Pattern of relapse	From index date to date to progression or death or date of enrollment in the study (up to 5 years)	Patterns of relapse after durvalumab treatment (e.g., thoracic/extra-thoracic/central nervous system - CNS relapse).
Duration of platinum-etoposide chemotherapy	From index date until durvalumab maintenance initiation or death or discontinuation of treatment (up to 5 years)	Duration of platinum-etoposide chemotherapy prior to durvalumab maintainance initiation
durvalumab treatment duration	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)	durvalumab treatment duration
number of durvalumab administrations	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)	number of durvalumab administrations
reason for durvalumab dosage adjustment	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)	reason for durvalumab dosage adjustment
reason for temporary interruption or permanent discontinuation	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)	reason for temporary interruption or permanent discontinuation of durvalumab, (e.g., safety event)
Concomitant tratments	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)	Details of chemotherapy (platinum-etoposide) combined with durvalumab and other concomitant treatments.
Subsequent anticancer treatments	From discontinuation of durvalumab until death or date of enrollment in the study (up to 5 years)	Details of subsequent anticancer treatments; treatment sequences over time for ES-SCLC.
Adverse Event of Special interest (AESI)verbatim; severity; seriousness; causality; action taken with respect to durvalumab treatment; outcome.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP.
Adverse Event other than AESI (limited to Adverse Drug Reaction - ADR and Serious Adverse Event - SAE, including Serious Adverse Drug Reaction - SADR) verbatim; severity; seriousness; causality; action taken with respect to durvalumab treatment; outcome.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP.
Occurrence of at least one AESI/ ADR/ SAE/ SADR.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.
Durvalumab temporary interruption due to AESIs/ ADRs/SAEs/SADRs.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.
Durvalumab permanent discontinuation due to AESIs/ ADRs/SAEs/SADRs.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.

Trial Locations

Locations (1)

Research Site; 🇮🇹 Vimercate, Italy