Cambridge, UK — September 4, 2026
AstraZeneca announced that ETCAMAH® (camizestrant) in combination with a CDK4/6 inhibitor has received U.S. FDA accelerated approval for adults with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer following detection of an ESR1 mutation during aromatase inhibitor (AI) and CDK4/6 inhibitor therapy, based on an FDA-authorized test. The approval is supported by results from the pivotal SERENA-6 Phase III trial, which evaluated a ctDNA-guided treatment strategy designed to identify emerging endocrine resistance before radiographic or clinical disease progression. In a planned interim analysis, the ETCAMAH combination reduced the risk of disease progression or death by 56% compared with continued AI plus CDK4/6 inhibitor therapy, with a hazard ratio of 0.44 and median progression-free survival of 16.0 months versus 9.2 months. The approval represents a significant development for AstraZeneca’s breast cancer portfolio and introduces a treatment strategy intended to enable an earlier therapeutic switch when an ESR1 resistance mutation emerges.
AstraZeneca Advances ctDNA-Guided Treatment Strategy
The SERENA-6 Phase III trial enrolled 315 patients with HR-positive, HER2-negative advanced breast cancer whose tumors developed an emergent ESR1 mutation while receiving first-line AI and CDK4/6 inhibitor therapy. Rather than waiting for clinical or radiographic progression, the trial used circulating tumor DNA (ctDNA) monitoring through blood testing performed alongside routine tumor assessments to identify the emergence of ESR1 mutations. Patients with an emerging mutation but no evidence of disease progression were switched from their ongoing AI to ETCAMAH while continuing the same CDK4/6 inhibitor. This approach is intended to address endocrine resistance at an earlier stage of disease evolution. AstraZeneca said the strategy could potentially reshape the first-line treatment paradigm by using molecular evidence of resistance to guide treatment decisions before conventional indicators of progression become apparent. The FDA simultaneously approved a companion diagnostic test for detecting emerging ESR1 resistance mutations in ctDNA, supporting the biomarker-guided use of ETCAMAH.
ETCAMAH Demonstrates Progression-Free Survival Benefit
The clinical results supporting the approval showed a substantial benefit in progression-free survival (PFS) for patients receiving ETCAMAH with a CDK4/6 inhibitor. The combination produced a 56% reduction in the risk of disease progression or death, with a hazard ratio of 0.44 and a highly statistically significant p-value of less than 0.00001. Subsequent pre-planned analysis also demonstrated a statistically significant benefit in PFS2, with median PFS2 of 25.7 months for the ETCAMAH combination compared with 19.1 months for the standard-of-care arm, corresponding to a hazard ratio of 0.63. Overall survival data remained immature and continue to be evaluated as a key secondary endpoint. The safety profile of ETCAMAH combined with palbociclib, ribociclib, or abemaciclib was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified in SERENA-6. AstraZeneca highlighted the treatment as an innovative approach for patients whose tumors develop ESR1 mutations during first-line endocrine therapy.
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AstraZeneca Expands ETCAMAH Breast Cancer Development
ETCAMAH (camizestrant) is an oral next-generation selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist designed to target ER-driven breast cancer. The recommended dose in combination with a CDK4/6 inhibitor is 75 mg once daily. The U.S. approval adds to ETCAMAH’s regulatory expansion, with the medicine also approved in the EU, Japan and several other countries based on SERENA-6 results. AstraZeneca is continuing a broad clinical development program for ETCAMAH, including the SERENA-4, CAMBRIA-1 and CAMBRIA-2 Phase III trials, evaluating its potential as monotherapy and in combination with CDK4/6 inhibitors across additional HR-positive, HER2-negative breast cancer settings. The company is positioning the therapy as part of its wider effort to address endocrine resistance and improve outcomes in breast cancer. With ESR1 mutations emerging as an important mechanism of resistance to endocrine treatment, the FDA approval gives clinicians a new biomarker-guided treatment option while reinforcing AstraZeneca’s focus on molecularly informed approaches to HR-positive breast cancer care.
Source: AstraZeneca, press relese
