In certain patients with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer, switching from an aromatase inhibitor (AI) to camizestrant (AstraZeneca) while continuing with a CDK4/6 inhibitor, can extend the benefit of first-line therapy. This was shown in patients for whom an ESR1 mutation was detected before disease progression.
This conclusion comes from the SERENA-6 study presented at the ASCO Annual Meeting 2025 (LBA4), in Chicago.
SERENA-6 recruited 3,256 patients with at least six months on a first-line AI and CDK4/6 inhibitor. Under ctDNA surveillance, 548 patients had ESR1 mutations detected and 315 were randomized to two groups. The first group switched from an AI to camizestrant, continuing with the CDK4/6 inhibitor and adding placebo in place of the AI (157 patients). The second group continued the AI and CDK4/6 inhibitor, adding placebo in place of camizestrant (158 patients).
The median progression-free survival (PFS) was 16 months for those who switched to camizestrant and 9.2 months for those who continued with an AI (hazard ratio, 0.44; 95% CI, 0.31-0.60; P<0.00001). The PFS rate at 12 months was 60.7% in the camizestrant arm versus 33.4%, and at 24 months was 29.7% in the camizestrant arm versus 5.4%. Quality of life deteriorated at six months with AI continuation and 23 months with the camizestrant switch.
Nicholas C. Turner, MD, PhD, from the Royal Marsden Hospital, in London, noted that SERENA-6 demonstrates the clinical utility of ctDNA monitoring to detect and treat emerging resistance ahead of disease progression. This represents a potential new treatment strategy in oncology to treat developing resistance before it causes progression, he noted.
At a press conference, Eleonora Teplinsky, MD, the head of breast and gynecologic medical oncology at Valley-Mount Sinai Comprehensive Cancer Care in Paramus, N.J., provided perspective. “This study [details] an early-switch approach before we see disease progression on imaging, allowing us to essentially stay ahead of the curve,” she said. Outcomes worsen with subsequent lines of therapy, so enabling patients to remain on first-line endocrine therapy for longer is significant, she added. “[Camizestrant] also improves quality of life … and that is a huge, huge part of living with metastatic breast cancer.”
Dr. Teplinsky said although camizestrant is not yet FDA-approved, it likely will offer a new strategy in first-line HR+, HER2– metastatic breast cancer in patients with ESR1 mutations.
Dr. Teplinsky reported financial relationships with AbbVie, Daiichi Sankyo/AstraZeneca, Immunogen, Novartis, Pfizer and Sermo. Dr. Turner reported financial relationships with AstraZeneca, Exact Sciences, Gilead Sciences, GlaxoSmithKline, Guardant Health, Inivata, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Relay Therapeutics, Repare Therapeutics and Roche.
This article is from the August 2025 print issue.