Reference: August 2025 | Issue 8 | Vol 11 | Page 5
The SERENA-6 phase 3 trial has reported that camizestrant in combination with a CDK 4/6 inhibitor achieves a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with HR-positive HER2-negative advanced breast cancer who develop ESRI1 mutations during first-line treatment with an aromatase inhibitor (AI).
SERENA-6 enrolled 3,256 patients with HR-positive, HER2-negative advanced breast cancer who had received at least six months of treatment with an AI (letrozole or anastrozole) and a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib).
Patients were randomly assigned to either:
- Switch from treatment with an AI to camizestrant and continue with the CDK4/6 inhibitor, adding a placebo in place of the AI (n=157), or
- Continue treatment with an AI and CDK4/6 inhibitor, adding a placebo in place of camizestrant (n=158).
Patients had their circulating tumour DNA (ctDNA) tested for ESR1 mutations every two to three months until 315 patients developed ESR1 mutations before disease progression. About 50 per cent of these patients had an ESR1 mutation detected during the first ctDNA test. This is significant as testing for ESR1 mutations is typically not done until the cancer has already started to progress.
The results of the trial, presented at ASCO 2025, showed that median PFS was 16 months for those who switched to camizestrant vs. 9.2 months for those who continued treatment with an AI. One year after treatment, PFS was 60.7 per cent in the camizestrant group vs. 33.4 per cent in the AI group.
At two years, PFS was 29.7 per cent vs 5.4 per cent, respectively. The PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups, including analysis by age, race, region, time of ESR1 mutation detection, and type of ESR1 mutation.
The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life. The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination versus 6.4 months in patients that continued treatment with the AI combination. The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination. Overall survival data are still awaited.
The rate of adverse event-related treatment discontinuation was 1.3 per cent in the camizestrant group vs 1.9 per cent in the AI group.
SERENA-6 is the first pivotal trial to demonstrate the clinical value of monitoring ctDNA to detect and treat emerging resistance in first-line therapy before disease progression in breast cancer, and camizestrant is the first and only next-generation oral SERD and complete ER antagonist to demonstrate consistent PFS benefit in combination with CDK4/6 inhibitors in the first-line treatment of advanced breast cancer.
Commenting on the findings, lead study author Nicholas C Turner from the Royal Marsden Hospital in London, said: “Following progression of disease on first-line therapy for advanced HR-positive breast cancer, a number of treatment options exist. However, their benefit is limited; quality of life decreases, and survival rates are low. Patients have an urgent need for new treatments that can prolong time on first-line therapy and delay disease progression. The results from SERENA-6 represent an important step forward and a potential new treatment strategy to improve first-line outcomes for patients.”
Reference
Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. ASCO 2025. Abstract #LBA4. American Society of Clinical Oncology Annual Meeting. May 30-June 3, 2025. Chicago, US.
