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Jump to Key Points The FDA has granted accelerated approval to camizestrant (Etcamah, AstraZeneca), in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) for adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer upon detection of an ESR1 mutation during aromatase inhibitor (AI) and CDK4/6 inhibitor therapy, on the basis of an FDA-authorized test.
The agency also approved Guardant360 CDx, a circulating tumor DNA (ctDNA) assay, to detect the mutation. It’s the first time the FDA has approved a change in cancer treatment on the basis of ctDNA testing instead of disease progression on imaging, the agency said in a press release.
About 30% of patients develop ESR1 mutations during upfront AI and CDK4/6 inhibitor treatment, which causes resistance to the AI. The approval allows the AI to be switched to camizestrant, an oral selective estrogen receptor degrader, once the mutation is detected.
In April, the FDA’s Oncologic Drugs Advisory Committee voted 6-3 against approval. Among the objections, some panelists said there was no evidence that outcomes improve if the switch to camizestrant is made sooner, based on ctDNA testing instead of radiographic progression. The approval study, SERENA-6, did not directly compare the two strategies.
- FDA accelerated approval: camizestrant + CDK4/6 inhibitor for ESR1-mutated HR+/HER2- advanced breast cancer.
- Use after AI + CDK4/6 therapy when ESR1 mutation detected by FDA-authorized ctDNA test.
- Guardant360 CDx approved; first FDA cancer treatment change based on ctDNA, not imaging progression.
- SERENA-6: PFS 16 vs 9.2 months; QoL deterioration delayed 21 vs 6.4 months.
- Boxed warning: QTc prolongation; also bradycardia and embryo-fetal toxicity warnings.
FDA acknowledged that concern in announcing the approval, saying it has required confirmatory studies to “verify and describe clinical benefit.”
SERENA-6 included 315 patients with ESR1 mutations who had been on an AI and a CDK4/6 inhibitor for at least 6 months. They were randomly assigned evenly to either continue the AI or switch to camizestrant, both while remaining on the CDK4/6 inhibitor.
Overall, the switch to camizestrant improved progression-free survival to a median of 16 months vs 9.2 months with continued AI treatment. Median time to deterioration in patient-reported global health status and quality of life was 21 months and 6.4 months, respectively. Overall survival data were immature at the time of the analysis.
Prescribing information includes a boxed warning on QTc interval prolongation when used with other drugs that prolong the QTc interval, as well as warnings and precautions for bradycardia and embryo-fetal toxicity.
The recommended camizestrant dose is 75 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. The CDK4/6 inhibitor continues at the same dose as when the ESR1 mutation was detected.
M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net
