First-line camizestrant for ESR-1 mutated advanced breast cancer

In patients with estrogen receptor-positive, HER2-negative advanced breast cancer with an ESR-1 mutation that emerged during treatment, switching to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy leads to significantly longer progression-free survival than maintaining an aromatase-inhibitor combination, as shown by SERENA-6 trial results recently published on the New England Journal of Medicine.

In the phase 3 SERENA trial, a total of 3256 patients with advanced breast cancer with ER-positive, HER2–negative tumors receiving a first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor were tested for ESR-1 mutations in circulating tumor DNA once every 2 to 3 months. The 315 patients with ESR-1 mutated tumor were randomized to switch to the next-generation selective ER degrader and complete ER antagonist camizestrant or maintain an aromatase inhibitor. At a median follow-up of 12,6 months, the median progression-free survival was 16 months in the camizestrant group and 9.2 months in the aromatase-inhibitor group; the median time until a deterioration in the patient-reported global health status and quality of life occurred was 23 months with camizestrant and 6.4 months with an aromatase inhibitor, whereas frequency of discontinuation because of adverse events were similar. «Switching first-line therapy to camizestrant while continuing the administration of a CDK4/6 inhibitor after the detection of an ESR-1 mutation and ahead of disease progression resulted in significantly longer progression-free survival than continuing with first-line therapy with an aromatase-inhibitor plus a CDK4/6 inhibitor in patients with ER-positive, HER2-negative advanced breast cancer», authors say. «These results support the proactive switch to camizestrant as compared with the continuation of an aromatase inhibitor and emphasize the importance of avoiding progression during first-line therapy. We also established the clinical utility of using circulating tumor DNA monitoring to detect and treat emerging resistance before disease progression, which may represent a potentially new treatment strategy», authors conclude.