First-Line Camizestrant for Emerging <i>ESR1</i> -Mutated Advanced Breast Cancer
François‐Clément Bidard, Erica L. Mayer, Yeon Hee Park, Wolfgang Janni, X. Cynthia, Massimo Cristofanilli, Giampaolo Bianchini, Kevin Kalinsky, Hiroji Iwata, Stephen Chia, Peter A. Fasching, Adam Brufsky, Zbigniew Nowecki, Javier Pascual, L. Moreau, Shin-Cheh Chen, Nuri Karadurmuş, Einav Nili Gal‐Yam, Kyung Hae Jung, Sònia Pernas, Sasha McClain, Wei He, Teresa Klinowska, Cynthia Huang Bartlett, Nicholas C. Turner
Abstract
BACKGROUND: are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer. METHODS: mutation and did not have radiologic progression were assigned in a 1:1 ratio to switch to camizestrant (75 mg once daily) with a continued CDK4/6 inhibitor plus placebo in place of an aromatase inhibitor or to continue to receive an aromatase inhibitor plus a CDK4/6 inhibitor plus placebo in place of camizestrant. The primary outcome was investigator-assessed progression-free survival. RESULTS: mutation. The 315 eligible patients were assigned to switch to camizestrant (157 patients) or to continue to receive an aromatase inhibitor (158 patients). At an interim analysis at a median follow-up of 12.6 months, the median progression-free survival was 16.0 months (95% confidence interval [CI], 12.7 to 18.2) in the camizestrant group and 9.2 months (95% CI, 7.2 to 9.5) in the aromatase-inhibitor group (hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P<0.0001). The median time until a deterioration in the patient-reported global health status and quality of life occurred was 21.0 months with camizestrant and 6.4 months with an aromatase inhibitor (hazard ratio, 0.54; 95% CI, 0.34 to 0.84). The frequency of discontinuation because of adverse events was 1.3% with camizestrant and 1.9% with an aromatase inhibitor. CONCLUSIONS: mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).