CHMP adopted a positive opinion on camizestrant at its May 18-21 meeting, recommending Etcamah for ER-positive, HER2-negative advanced breast cancer with an emergent ESR1 mutation. That landed weeks after FDA’s ODAC voted 3 to 6 against the same application.
The split isn’t about efficacy. The SERENA-6 Phase III trial cut the risk of disease progression or death by 56% versus standard aromatase inhibitor therapy (HR 0.44), with median progression-free survival of 16.0 months against 9.2. ODAC’s objection turned on trial design: SERENA-6 used circulating tumor DNA monitoring to detect emergent ESR1 mutations before clinical progression, then switched patients to camizestrant plus a CDK4/6 inhibitor. Under the old yardstick, treatment switches waited for progression on scan or symptoms. SERENA-6 did it on a ctDNA signal. The committee couldn’t validate that trigger as a basis for approval.
After the ODAC no-vote, CHMP held a formal oral explanation session, EMA’s mechanism for pressing on contested data. I read the May 22 meeting highlights: the committee concluded in favor, for adults without disease progression during first-line endocrine therapy combined with a CDK4/6 inhibitor. AstraZeneca said it will “continue to work with the FDA” as the agency completes its review.
The divergence maps a real regulatory philosophy split. SERENA-6’s ctDNA-guided switch design is a template other breast cancer sponsors are watching. If ODAC’s skepticism holds, it creates a headwind for the entire class of biomarker-adaptive switch trials — regardless of how clean the efficacy data looks. CHMP’s endorsement says EMA is prepared to accept novel trial architecture. FDA hasn’t said that yet.
The ODAC vote is advisory; the agency makes its own call. Worth tracking SERENA-6’s FDA review minutes before you draft any ctDNA-guided switch protocol this year.
Rebecca Lauren