Fulvestrant
- Generic Name
- Fulvestrant
- Brand Names
- Faslodex, Fulvestrant Mylan
- Drug Type
- Small Molecule
- Chemical Formula
- C32H47F5O3S
- CAS Number
- 129453-61-8
- Unique Ingredient Identifier
- 22X328QOC4
- Background
Fulvestrant is a drug treatment of hormone receptor (HR)-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. While it is used as monotherapy for the treatment of breast cancers, it is also used in combination with alpelisib for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer
- Indication
For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy, as monotherapy or in combination with other antineoplastic agents.
- Associated Conditions
- Advanced Breast Cancer, Advanced or Metastatic Breast Cancer
AstraZeneca Halts Phase 3 Trial of Capivasertib for Metastatic Castration-Resistant Prostate Cancer
• AstraZeneca has discontinued the Phase 3 CAPItello-280 trial evaluating Truqap (capivasertib) plus docetaxel and ADT in metastatic castration-resistant prostate cancer after an independent monitoring committee determined the treatment was unlikely to meet primary endpoints.
• The trial involved 1,033 patients and was designed to validate earlier promising results from the Phase 2 ProCAID trial, which had shown extended overall survival with capivasertib in patients who received prior androgen receptor-targeted therapy.
• Despite the setback in prostate cancer, Truqap remains approved in multiple countries for HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations following progression on endocrine-based regimens.
Breakthrough Breast Cancer Drug Capivasertib Approved for NHS Use
• A groundbreaking twice-daily pill called capivasertib (Truqap) has been approved for NHS use, targeting hormone receptor-positive HER2-negative breast cancer by blocking cancer growth mechanisms.
• Clinical trials demonstrated the drug extends time before cancer progression by over four months when used alongside hormone therapy Fulvestrant, offering new hope for approximately 3,000 women annually.
• The treatment specifically benefits patients with PIK3CA, AKT1 or PTEN gene mutations, allowing many to maintain good quality of life with fewer debilitating side effects compared to other treatment regimens.
Eagle Pharmaceuticals Secures $69 Million Deal to Monetize BENDEKA Royalties
• Eagle Pharmaceuticals has entered into a $69 million royalty purchase agreement with Blue Owl Capital to sell its royalty interest in BENDEKA, a treatment for chronic lymphocytic leukemia and non-Hodgkin lymphoma.
• The non-dilutive capital will be used to repay $52.5 million in existing debt, with remaining proceeds allocated to general corporate purposes and ongoing R&D programs.
• Eagle continues to invest in its pipeline, including CAL02 for severe community-acquired bacterial pneumonia and EA 114, a novel formulation of Fulvestrant for hormone-receptor-positive metastatic breast cancer.
Novel BCMA-Directed CAR T-Cell Therapy Shows Promising Efficacy in Relapsed/Refractory Multiple Myeloma and AL Amyloidosis
• A second-generation BCMA-directed CAR T-cell therapy, MDC-CAR-BCMA001, demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma and AL amyloidosis, achieving a 5/6 overall response rate with 4 complete responses.
• The novel therapy showed a favorable safety profile with manageable toxicity, including low incidence of severe cytokine release syndrome and no neurotoxicity, even in patients with significant organ dysfunction.
• These promising results have prompted further investigation through ongoing clinical trials, including CARLOTTA001 (NCT05836896) and the CLEAR AL trial, potentially offering new hope for difficult-to-treat hematologic malignancies.
ESR1 Mutations in Breast Cancer: Emerging Biomarker Reshapes Treatment Strategies
• ESR1 mutations are rare (<5%) in newly diagnosed breast cancer but develop in 30-40% of patients after aromatase inhibitor therapy, enabling tumors to remain active without estrogen.
• Circulating tumor DNA testing for ESR1 mutations is typically performed at disease progression, but emerging research suggests earlier detection could optimize treatment decisions.
• The presence of ESR1 mutations helps guide therapy selection, with oral selective estrogen receptor degraders like elacestrant showing improved efficacy compared to standard treatments.
FDA-Approved Itovebi Combination for Advanced Breast Cancer Requires Careful Blood Sugar Monitoring
• The FDA has approved Itovebi in combination with Ibrance and Faslodex for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer, based on the INAVO120 trial results.
• Healthcare providers must carefully monitor blood sugar levels in patients receiving Itovebi, as the PIK3CA pathway affects glucose metabolism and can cause hyperglycemia.
• Treatment success requires a coordinated approach involving oncologists, endocrinologists, nurses, and pharmacists, particularly for patients with pre-existing diabetes.
Alzheon to Present Phase 3 Data for ALZ-801, Aiming to Slow Alzheimer's Progression
• Alzheon is set to present Phase 3 trial data for ALZ-801 in April 2025, a drug designed to prevent the formation of toxic beta-amyloid plaques in early Alzheimer's patients with the ApoE4 gene.
• Anavex Life Sciences has submitted blarcamesine for approval in Europe after completing Phase 2/3 trials, though its efficacy has faced criticism and legal challenges.
• Athira Pharma discontinued fosgonimeton development after failing to demonstrate clinical benefit and settled with the DOJ over data manipulation allegations.
• Eisai and Biogen's Leqembi may become more accessible with an injectable version under FDA review, potentially allowing for at-home administration.
Datopotamab Deruxtecan's Role in HR+/HER2- Breast Cancer Treatment: Sequencing and Safety Considerations
• Datopotamab deruxtecan (Dato-DXd) is poised to become a standard treatment for metastatic hormone receptor-positive, HER2-negative breast cancer after prior systemic therapy.
• Optimal sequencing of antibody-drug conjugates (ADCs) like Dato-DXd, sacituzumab govitecan, and trastuzumab deruxtecan remains uncertain, especially considering overlapping toxicities.
• Real-world toxicity profiles suggest sacituzumab govitecan may cause more cytopenias and diarrhea, while Dato-DXd and trastuzumab deruxtecan are linked to interstitial lung disease.
• The lack of overall survival difference in the TROPION-Breast01 trial raises questions about efficacy issues or the impact of crossover between treatment arms.
Lerociclib Plus Fulvestrant Shows Promise in HR+/HER2- Advanced Breast Cancer
• The LEONARDA-1 phase 3 trial demonstrated that lerociclib plus fulvestrant significantly improved progression-free survival (PFS) compared to placebo plus fulvestrant in patients with HR+/HER2- advanced breast cancer.
• The combination of lerociclib and fulvestrant showed a manageable safety profile, with hematological toxicities being the most common adverse events, effectively managed with dose adjustments.
• Lerociclib plus fulvestrant exhibited efficacy across various patient subgroups, including those with primary endocrine therapy resistance and liver metastasis, addressing a critical unmet need.
• The study supports lerociclib plus fulvestrant as a potential treatment option for patients with HR+/HER2- advanced breast cancer who have progressed on prior endocrine therapy.
Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones
• Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer, one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 inhibitor.
• Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer is anticipated in the first quarter of 2025.
• Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas and file an IND application for a novel PROTAC KRAS G12D degrader in 2025.
• Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease has been initiated, with data expected to be presented in the first half of 2025.
Bayer's Elinzanetant Shows Promise in Reducing Hot Flashes for Breast Cancer Patients
• Elinzanetant met primary endpoints in the Phase III OASIS 4 trial, significantly reducing the frequency of moderate to severe vasomotor symptoms (VMS) in women undergoing endocrine therapy for breast cancer.
• The study also achieved secondary endpoints, demonstrating a reduction in the severity of VMS, improvements in sleep disturbances, and enhanced menopause-related quality of life compared to placebo.
• Elinzanetant is a dual neurokinin-1 and 3 receptor antagonist, representing a potential non-hormonal treatment option for VMS in breast cancer patients and women at high risk.
• Bayer is advancing regulatory submissions for elinzanetant in the US, EU, and other global markets, with potential launch expected later this year, pending regulatory approvals.
Enhertu Approved for HER2-Low and HER2-Ultralow Metastatic Breast Cancer
• The FDA has approved Enhertu for HR-positive, HER2-low or HER2-ultralow metastatic breast cancer after endocrine therapy progression.
• DESTINY-Breast06 trial data showed a 36% reduction in disease progression or death risk compared to chemotherapy.
• Patients on Enhertu had a median progression-free survival of 13.2 months versus 8.1 months on chemotherapy.
• This approval expands Enhertu's use to an earlier treatment setting and a broader patient population.
Datroway (Datopotamab Deruxtecan) Receives Global Approvals for Advanced Breast Cancer
• Datroway (Dato-DXd) gains first global approval in Japan for previously treated, unresectable, or recurrent HR-positive, HER2-negative breast cancer, offering a new alternative to conventional chemotherapy.
• The FDA has approved Datroway for advanced breast cancer, marking the first U.S. approval for the antibody-drug conjugate developed by AstraZeneca and Daiichi Sankyo.
• EMA endorsed Dato-DXd as a late-line option for certain breast cancer cases, adding to approvals in the U.S. and Japan and expanding treatment options in Europe.
• Clinical trials, including TROPION-Breast01, demonstrated that Datroway significantly delayed cancer progression compared to standard chemotherapy, with manageable safety profiles.
340B Drug Program Faces Scrutiny Over Hospital Markups and Transparency Issues in Cancer Care
• The 340B Drug Pricing Program has expanded from 1,000 covered entities in 1992 to over 50,000 in 2021, with hospitals marking up oncology drugs by nearly 5 times their acquisition costs.
• Healthcare consolidation trends show 81.6% of hospital acquisitions were made by 340B-covered entities, potentially increasing patient care costs by shifting treatment to more expensive hospital settings.
• New legislation, the 340B ACCESS Act, has been introduced to address transparency issues and ensure the program serves its original purpose of providing affordable medications to underserved populations.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
Advancements in Breast Cancer Research Unveiled at SABCS 2024
• The PATINA trial suggests palbociclib with anti-HER2 and endocrine therapy may become a new standard for HR+, HER2+ metastatic breast cancer.
• COMET trial indicates active monitoring is comparable to surgery for low-risk DCIS, offering a potential alternative management option.
• OlympiA trial's long-term results reinforce olaparib's role in preventing recurrence and highlight the importance of BRCA testing for early-stage breast cancer.
Gilead's Trodelvy Receives FDA Breakthrough Therapy Designation for SCLC; Seladelpar Recommended for EU Approval
• The FDA granted Breakthrough Therapy Designation to Gilead's Trodelvy for extensive-stage small cell lung cancer (ES-SCLC) after platinum-based chemotherapy, based on promising results from the TROPiCS-03 study.
• Gilead will collaborate with Terray Therapeutics to discover and develop novel, small molecule therapies across multiple targets, leveraging Terray's tNova platform.
• The European Medicines Agency's CHMP recommended approval of Gilead's seladelpar for primary biliary cholangitis (PBC) in combination with UDCA or as monotherapy.
Imlunestrant Shows Promise in Advanced ER+/HER2- Breast Cancer Treatment
• Imlunestrant monotherapy significantly improved progression-free survival (PFS) in advanced breast cancer patients with ESR1 mutations compared to standard endocrine therapy.
• The combination of imlunestrant and abemaciclib demonstrated a statistically significant improvement in PFS compared to imlunestrant alone, regardless of ESR1 mutation status.
• The EMBER-3 trial results suggest imlunestrant, particularly in combination with abemaciclib, could offer a new all-oral targeted therapy option for pre-treated advanced breast cancer.
• Safety data from the trial indicated that imlunestrant, both as a monotherapy and in combination, was generally well-tolerated, with manageable adverse events.
DATROWAY® (Datopotamab Deruxtecan) Receives EU Approval for Previously Treated Metastatic HR+/HER2- Breast Cancer
• DATROWAY, a TROP2-directed antibody drug conjugate (ADC), has been approved in the European Union for treating adult patients with unresectable or metastatic HR+/HER2- breast cancer who have received endocrine therapy and at least one line of chemotherapy.
• The approval is based on the TROPION-Breast01 phase 3 trial, which showed DATROWAY reduced the risk of disease progression or death by 37% compared to chemotherapy, with a median PFS of 6.9 months versus 4.9 months.
• This marks the second ADC approved for breast cancer based on Daiichi Sankyo's DXd technology and the third medicine from their oncology pipeline to receive EU approval, highlighting their commitment to developing innovative cancer treatments.
Real-World Data Suggests Elacestrant Offers Similar or Improved Outcomes in Advanced Breast Cancer
• A real-world analysis shows elacestrant demonstrates similar or slightly higher time to treatment discontinuation compared to the EMERALD trial.
• The median real-world time to next treatment with elacestrant was 6.43 months, and time to treatment discontinuation was 4.6 months.
• Patients with PIK3CA pathway alterations experienced worse outcomes with elacestrant, underscoring the need for precision medicine.
• Most patients received elacestrant beyond the second line of treatment, with outcomes remaining consistent across different lines of therapy.
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