WILMINGTON, DE — AstraZeneca’s (NYSE: AZN) ETCAMAH (camizestrant) combination won accelerated U.S. approval for certain advanced breast cancer patients whose tumors develop an ESR1 mutation during first-line therapy, allowing treatment to change before clinical or radiographic disease progression.
The Food and Drug Administration approved ETCAMAH in combination with a CDK4/6 inhibitor — abemaciclib, palbociclib or ribociclib — for adults with hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer after an ESR1 mutation is detected during treatment with an aromatase inhibitor and CDK4/6 inhibitor.
The approval is based on AstraZeneca’s Phase III SERENA-6 trial, which used circulating tumor DNA monitoring to identify emerging ESR1 mutations before disease progression.
In a planned interim analysis, ETCAMAH combined with a CDK4/6 inhibitor reduced the risk of disease progression or death by 56% compared with continued treatment using the aromatase inhibitors anastrozole or letrozole plus a CDK4/6 inhibitor. Median progression-free survival was 16 months with ETCAMAH versus 9.2 months with standard treatment.
A subsequent planned analysis found median time to second disease progression of 25.7 months with the ETCAMAH combination compared with 19.1 months for the control group. Overall survival data remain immature, and the trial will continue to assess that measure as a key secondary endpoint.
The FDA concurrently approved a companion diagnostic designed to detect emerging ESR1 resistance mutations in circulating tumor DNA.
SERENA-6 used blood testing during routine tumor scans every two to three months. When an ESR1 mutation emerged without disease progression, patients switched from their existing aromatase inhibitor to ETCAMAH while remaining on the same CDK4/6 inhibitor.
“The 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,” Kevin Kalinsky, division director of medical oncology at Winship Cancer Institute of Emory University and a trial investigator, stated.
ESR1 mutations are associated with resistance to endocrine therapy and can emerge as breast cancer is treated. AstraZeneca reported that about 30% of patients with endocrine-sensitive, HR-positive disease develop the mutations during first-line treatment before disease progression.
The safety profile of ETCAMAH combined with palbociclib, ribociclib or abemaciclib was consistent with the known profiles of the individual medicines, according to the trial results. No new safety concerns were identified, and discontinuation rates were low and similar between the study groups.
About 37,000 U.S. patients with HR-positive metastatic breast cancer receive first-line drug treatment, according to AstraZeneca. Endocrine therapies targeting estrogen receptor-driven disease are frequently paired with CDK4/6 inhibitors, but resistance can develop during treatment.
The ETCAMAH approval is AstraZeneca’s 10th FDA approval this year across its portfolio and its fourth involving breast cancer, according to Dave Fredrickson, executive vice president of the company’s Oncology Haematology Business Unit.
ETCAMAH is also approved in more than 30 countries, including the European Union, Japan, Canada and the UK, based on the SERENA-6 trial.
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