The European Medicines Agency’s human-medicines committee has recommended marketing authorisation for AstraZeneca’s camizestrant (Etcamah), an oral selective estrogen-receptor degrader, for ER-positive, HER2-negative advanced breast cancer driven by an emerging ESR1 mutation. The positive opinion, issued at the CHMP’s 18-21 May 2026 meeting, covers use in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in patients whose tumours acquire an ESR1 mutation but have not yet progressed on first-line endocrine therapy plus a CDK4/6 inhibitor.

The recommendation rests on SERENA-6, a phase III, double-blind, randomised trial that tested a novel idea: act on resistance before a scan shows it. ESR1 mutations are the most common acquired-resistance mechanism to aromatase-inhibitor-based therapy, and they surface in circulating tumour DNA (ctDNA) before radiologic progression.

A molecular trigger, not a radiologic one

Investigators screened 3,256 patients with ctDNA testing every two to three months. The 315 who had a detectable ESR1 mutation without radiologic progression were randomised 1:1 to switch to camizestrant while continuing the same CDK4/6 inhibitor (157 patients), or to stay on their aromatase inhibitor plus CDK4/6 inhibitor (158 patients).

On the primary endpoint, investigator-assessed progression-free survival, median PFS was 16.0 months (95% CI, 12.7 to 18.2) with camizestrant versus 9.2 months (95% CI, 7.2 to 9.5) with the continued aromatase inhibitor — a hazard ratio for progression or death of 0.44 (95% CI, 0.31 to 0.60; P<0.0001) at a median follow-up of 12.6 months.

Median progression-free survival reached 16.0 months with camizestrant versus 9.2 months on the continued aromatase inhibitor.

A secondary patient-reported endpoint also favoured the switch: median time to deterioration in global health status and quality of life was 21.0 months versus 6.4 months (hazard ratio, 0.54; 95% CI, 0.34 to 0.84). Few patients stopped treatment because of adverse events: 1.3% of camizestrant-treated patients and 1.9% of aromatase-inhibitor-treated patients discontinued for that reason.

One caveat carries weight. SERENA-6 read out at an interim analysis, and overall survival was immature. Independent commentators have noted that it remains unproven whether switching at molecular progression improves long-term outcomes versus switching at conventional clinical progression. A CHMP positive opinion is a recommendation; a European Commission decision on the marketing authorisation follows.