Dr Mayer on the FDA Approval of Camizestrant for ESR1-Mutated Breast Cancer

“The approval of camizestrant based on the data from SERENA-6 is incredibly important, not only for the approval of the agent itself, but also for the overall platform and structure in which it was approved.”

Erica L. Mayer, MD, MPH, director of Breast Cancer Clinical Research in the Breast Oncology Program at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, discussed the FDA approval of the oral selective estrogen receptor degrader (SERD) camizestrant (Etcamah) plus a CDK4/6 inhibitor for the treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer.

On September 4, 2026, the FDA granted accelerated approval to camizestrant plus a CDK4/6 inhibitor (abemaciclib [Verzenio], palbociclib [Ibrance], or ribociclib [Kisqali]) for the treatment of adult patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer that acquires an ESR1 mutation during treatment with an aromatase inhibitor plus a CDK4/6 inhibitor, as identified by an FDA-approved companion diagnostic (the Guardant360 CDx assay). The approval was based on data from the phase 3 SERENA-6 trial (NCT04964934), in which switching to camizestrant improved the median progression-free survival (PFS) to 16.0 months (95% CI, 12.7-18.2) vs 9.2 months (95% CI, 7.2-9.5) with continued aromatase inhibition plus a CDK4/6 inhibitor (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).

This approval will play an important role in the evolution of the breast cancer clinical research paradigm, Mayer said. Camizestrant joins other novel endocrine agents that are approved for advanced hormone receptor–positive, HER2-negative breast cancer, she explained. It is well tolerated and, in combination with a CDK4/6 inhibitor, highly active, she noted.

One of the most notable contributions of the SERENA-6 trial has been the introduction of the concept of monitoring for the emergence of resistance mutations and tailoring treatment based on those findings, according to Mayer. In the trial, patients underwent serial circulating tumor DNA (ctDNA) monitoring during first-line therapy with an aromatase inhibitor and a CDK4/6 inhibitor. Patients who were found to have an emergent ESR1 mutation in the estrogen receptor were randomly assigned to continue to receive their current therapy or switch to camizestrant while continuing the CDK4/6 inhibitor.

Patients who made the switch experienced a prolongation in PFS and a delay in the deterioration of quality of life, Mayer said. There was additionally a delay in the time until a patient needed to switch to chemotherapy and an improvement in time to second progression (PFS2).

Beyond offering the camizestrant-based regimen to patients whose cancers develop an ESR1 resistance mutation, the approval more broadly introduces the concept of monitoring patients for resistance mutations and intervening at the time of molecular progression rather than waiting for clinical progression, Mayer said. She expressed hope that the approval will make a substantial difference in patients’ lives and improve their treatment outcomes.