The European Commission has approved AstraZeneca's Etcamah (camizestrant) in combination with a CDK4/6 inhibitor for adult patients with ER-positive, HER2-negative advanced breast cancer who develop ESR1 mutations. Based on the Phase III SERENA-6 trial, this regimen reduces the risk of disease progression or death by 56% compared to standard-of-care aromatase inhibitors. The approval marks a shift toward ctDNA-guided, pre-progression treatment switching to address emerging endocrine resistance.
Etcamah EU regulatory approval
- ▪Etcamah is also approved in Japan, the United Arab Emirates, and Saudi Arabia, while regulatory applications remain under review in other countries, including the United States.
- ▪The European Commission approved AstraZeneca's Etcamah (camizestrant) in combination with a CDK4/6 inhibitor for adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer with an ESR1 mutation and no disease progression during first-line endocrine therapy.
- ▪Etcamah is approved in the European Union for use in combination with any of the widely approved CDK4/6 inhibitors, including palbociclib, ribociclib, or abemaciclib.
SERENA-6 trial efficacy results
- ▪The SERENA-6 trial demonstrated a median progression-free survival of 16.0 months for the Etcamah combination compared to 9.2 months for the standard-of-care aromatase inhibitor combination.
- ▪A pre-planned analysis of the SERENA-6 trial showed a statistically significant second progression-free survival benefit of 25.7 months for the Etcamah combination versus 19.1 months for the comparator.
- ▪In the pivotal Phase III SERENA-6 trial, the Etcamah combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment with an aromatase inhibitor and a CDK4/6 inhibitor.
ctDNA-guided treatment switching
- ▪In the SERENA-6 trial, patients were monitored via blood-based circulating tumor DNA tests every two to three months to identify early signs of endocrine resistance through the emergence of ESR1 mutations.
- ▪Data presented at the American Society of Clinical Oncology meeting in June showed that patients switching to Etcamah had a median 99% reduction in ctDNA after eight weeks, with half achieving total ctDNA clearance.
- ▪The Phase III SERENA-6 trial is the first global registrational study to use a circulating tumor DNA-guided approach to detect endocrine resistance and switch therapy before radiographic disease progression.
ESR1 mutation endocrine resistance
- ▪Mutations in the ESR1 gene are a key driver of endocrine resistance in hormone receptor-positive breast cancer, emerging during treatment and becoming more prevalent as the disease progresses.
- ▪Approximately 30% of patients with endocrine-sensitive hormone receptor-positive breast cancer develop ESR1 mutations during first-line treatment before disease progression.
CDK4/6 inhibitor combination therapy
- ▪The safety profile of Etcamah in combination with palbociclib, ribociclib, or abemaciclib in the SERENA-6 trial was consistent with the known safety profile of each individual medicine, with very low discontinuation rates.
- ▪The recommended dose of Etcamah, a potent, next-generation oral selective estrogen receptor degrader and complete estrogen receptor antagonist, is 75mg administered orally once daily.
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