Camizestrant (oral SERD/complete ER antagonist) switch at emergent ESR1m extends PFS2 in 1L HR+/HER2− ABC (SERENA-6)

Camizestrant (CAMI) is a next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist tested in the Phase III, ctDNA-guided SERENA-6 switch strategy (NCT04964934): pts with HR+/HER2− advanced breast cancer on 1L aromatase inhibitor (AI) + CDK4/6 inhibitor without radiographic progression were randomized at emergent ESR1 mutation to switch endocrine backbone to CAMI while continuing the same CDK4/6i vs continue AI + CDK4/6i (n=157 vs 158). At data cutoff Jan 3, 2026 (median follow-up 23.5 mo), CAMI + CDK4/6i improved PFS2 to 25.7 vs 19.1 mo (HR 0.63, p=0.00373) and maintained the primary PFS benefit (16.8 vs 9.2 mo, HR 0.45; 30-mo PFS rate 30.4% vs 2.7%); it also prolonged chemo/ADC-free survival (22.6 vs 18.7 mo, HR 0.64; nominal p=0.00375) and delayed deterioration in global health status/QoL (TTD HR 0.48; nominal p<0.001). Safety was reported as consistent with prior reads (no new signal detailed here); the comparator reflects a common real-world “stay the course on AI + CDK4/6i until progression” approach, while the typical post-progression endocrine-only standard (e.g., elacestrant/fulvestrant) delivers much shorter median PFS in ESR1m disease (~3.8 mo in EMERALD), underscoring the value of preempting clinical progression rather than reacting after it.