Camizestrant Combination for Metastatic Breast Cancer Gains FDA Approval
The U.S. regulatory body has approved AstraZeneca’s Etcamah in combination with CDK4/6 inhibitors, to treat adults with HR‑positive, HER2‑negative metastatic breast cancer who are resistant to standard endocrine therapy.
FDA has cleared camizestrant (Etcamah) in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib). The therapeutic indication specified by the regulatory authority is for adults with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer whose tumors acquire an estrogen receptor 1 (ESR1) resistance mutation during first‑line treatment with an aromatase inhibitor (AI) and a CDK4/6 inhibitor — as identified by an FDA‑authorised companion diagnostic blood test (1).
The approval comes off the back of SERENA‑6, a global Phase III study that used serial circulating tumor DNA (ctDNA) monitoring to detect emerging ESR1 mutations to trigger an early switch from AI to camizestrant while maintaining the same CDK4/6 inhibitor. In a planned interim analysis, the camizestrant regimen cut the risk of disease progression or death by 56% versus continuing an AI plus CDK4/6 inhibitor. A later pre‑planned analysis also showed a statistically significant improvement in time to second progression (25.7 vs 19.1 months), while overall survival data continued to mature.
Around one in three patients with HR‑positive metastatic disease develop ESR1 mutations during first‑line endocrine therapy before radiographic progression, thus leading to poorer outcomes and limited subsequent options. By enabling clinicians to intervene at the molecular sign of resistance rather than waiting for tumor growth on scans, AstraZeneca argues the strategy can prolong benefit from endocrine therapy and delay the need for more toxic chemotherapy.
“This combination provides an important new option for the one in three patients with this form of advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression,” said Kevin Kalinsky, MD, MS, FASCO, Division Director of Medical Oncology, Winship Cancer Institute of Emory University and investigator for the trial, in an AstraZeneca press release (1). “[This] approval will enable clinicians to promptly intervene and change therapeutic strategy at an earlier opportunity ahead of disease progression, rather than waiting until the cancer becomes harder to treat, and patient outcomes and quality of life worsen.”
“[This] approval is the tenth granted by the FDA this year across AstraZeneca’s portfolio and our fourth in breast cancer alone,” added Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, in the press release (1). “The Etcamah combination reflects AstraZeneca’s leadership in redefining breast cancer care by pioneering a new approach using circulating tumor DNA and is the first and only medicine of its type in the 1st-line setting.”
Earlier in 2025, the FDA extended its review on the application after an oncology advisory committee failed to reach a clear majority in favor, citing questions over whether switching on ctDNA‑detected ESR1 mutations translates into robust long‑term benefit. AstraZeneca subsequently submitted additional analyses, including ctDNA clearance data tied to longer‑term efficacy, which were presented at ASCO 2026.
Camizestrant is a next‑generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist given once daily. Safety in SERENA‑6 was consistent with the known profiles of each drug, with low and similar discontinuation rates across arms. With more than 300,000 new breast cancer cases annually in the U.S. and only about a third of metastatic HR‑positive patients expected to live beyond five years, the approval adds a targeted option in a setting where resistance to standard endocrine therapy remains a major unmet need.
Reference
AstraZeneca. Etcamah in Combination with a CDK4/6 Inhibitor Approved in the US for 1st-line Advanced HR-Positive Breast Cancer. Press Release, Sept. 4, 2026.