AZN · AstraZeneca PLC

The FDA Oncologic Drugs Advisory Committee (ODAC) failed to achieve a majority vote in favor of AstraZeneca's camizestrant combined with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) for first-line treatment of HR-positive, HER2-negative advanced breast cancer patients with emergent ESR1 mutations, voting 3 to 6 against the benefit-risk profile. This decision follows positive SERENA-6 Phase III data presented at ASCO 2025 and published in NEJM, demonstrating a 56% reduction in risk of progression or death (HR 0.44, 95% CI 0.31-0.60, p<0.00001), with median PFS of 16.0 months versus 9.2 months for the aromatase inhibitor (AI) comparator arm. Additional analyses showed PFS2 benefit (25.7 vs 19.1 months, HR 0.63, p=0.00373) and quality of life improvements, including 46% reduced risk of deterioration in global health status (HR 0.54). Safety was consistent with known profiles, with low discontinuations. The innovative ctDNA-guided trial design detected ESR1 mutations early via blood tests, enabling therapy switch pre-progression. Despite the advisory vote, the FDA, which accepted the NDA in July 2025 after granting Breakthrough Therapy Designation in May 2025, is not bound by ODAC and will continue review. AstraZeneca expresses disappointment but confidence in the data, committing to collaboration with FDA. Regulatory filings are also pending in EU and Japan, underscoring camizestrant's potential in addressing ESR1-driven resistance in a patient population with limited options and poor prognosis.