Camizestrant Extends PFS and PFS2 in ESR1-Mutated Advanced Breast Cancer

The final progression-free survival 2 (PFS2) results from the phase 3 SERENA-6 trial (NCT04964934), demonstrating that proactively switching to camizestrant upon detection of emergent ESR1 mutations in patients receiving a first-line aromatase inhibitor (AI) plus CDK4/6 inhibitor (CDK4/6i) extended PFS by a median of 7.6 months compared with continuing the same AI-based regimen.¹

In the primary end point analysis, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, of the third data cutoff (DCO3; January 2, 2026) with a median follow-up of 23.5 months, camizestrant plus CDK4/6i reduced the risk of disease progression or death by 55% vs continued AI plus CDK4/6i (HR, 0.45; 95% CI, 0.34–0.59; nominal P <.00001). Median PFS was 16.8 months (95% CI, 14.7–19.4) with camizestrant vs 9.2 months (95% CI, 7.2–9.7) in the control arm, an absolute improvement of 7.6 months—up from the 6.8-month absolute improvement observed at the prior interim analysis.

At 24 months, 34.9% of patients in the camizestrant arm remained progression-free, compared with 14.2% in the AI continuation arm. The PFS benefit was consistent across common co-mutations, including PIK3CA (HR, 0.41; 95% CI, 0.26–0.64; median 18.2 vs 10.0 months) and TP53 co-mutations (HR, 0.52; 95% CI, 0.31–0.88; median 11.8 vs 5.6 months), and was similarly observed in patients harboring single (HR, 0.46; 95% CI, 0.34–0.62) or multiple (HR, 0.48; 95% CI, 0.25–0.88) ESR1 mutations.

The benefit with early switching persisted beyond first progression. PFS2—a pre-specified key secondary endpoint measuring time from randomization to second progression or death—reached statistical significance, with camizestrant plus CDK4/6i yielding a median PFS2 of 25.7 months (95% CI, 20.4–30.3) vs 19.1 months (95% CI, 16.8–21.0) in the control arm (HR, 0.63; 95% CI, 0.46–0.86; P=.00373), reflecting an absolute improvement of 6.6 months. A supplementary analysis per RECIST v1.1 criteria was consistent (HR, 0.64; 95% CI, 0.46–0.90), confirming that the clinical benefit of the early treatment switch was sustained even after patients received subsequent lines of therapy.

Camizestrant plus CDK4/6i also extended chemotherapy/ADC-free survival by a median of 3.9 months vs AI continuation (22.6 months [95% CI, 19.3–30.9] vs 18.7 months [95% CI, 15.8–22.1]; HR, 0.64; 95% CI, 0.47–0.87; nominal P=.00375), reflecting a meaningful delay in the need for more aggressive systemic therapy. Overall survival data remained immature at 30% maturity (information fraction 58%), but hazard ratios consistently favored camizestrant across all three data cuts (DCO3: HR, 0.87; 95% CI, 0.57–1.30), with confidence intervals continuing to narrow.

“AT DCO3, with longer follow-up, switching to camizestrant at emergence of ESR1 mutations, ahead of diease progression showed: median PFS improvement with camizestrant plus CDK4/6i….PFS2, a pre-specified key secondary end point, reached statistical significance,” Francoid-Clement Bidard, MD, PhD, professor of medicine in the Department of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, co-coordinator of Breast Cancer Research at Institut Curie, vice-chair of the French Breast Cancer research group UCBG (Unicancer), director of the Clinical Investigation Center at the Institut Curie and the medical director for Breast Oncology at the Women’s Cancer Institute, said during the presentation.

The randomized, double-blind, placebo-controlled phase 3 SERENA-6 trial enrolled adult patients with estrogen receptor–positive (ER+), HER2-negative advanced breast cancer who had received an AI plus a CDK4/6 inhibitor (palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio]) as their initial endocrine-based therapy for at least 6 months, had an ESR1 mutation detected in circulating tumor DNA (ctDNA) with no evidence of disease progression, and had received no more than 1 prior line of chemotherapy for advanced disease.

In total, 315 patients were randomly assigned 1:1 to camizestrant (75 mg once daily) plus continuing CDK4/6i and placebo for the AI (n=157) or to continuing AI plus CDK4/6i and placebo for camizestrant (n=158).

ctDNA dynamics corroborated the biologic activity of early treatment switching. Total ctDNA levels were profoundly reduced in the camizestrant arm, with a median 99% reduction at week 8 compared with a 64% increase in the AI plus CDK4/6i arm (Wilcoxon nominal P <.00001). Total ctDNA clearance by Guardant360 assay was achieved in 51% of evaluable patients in the camizestrant arm (50/98) vs 1.9% in the control arm (2/108). In a pooled exploratory analysis, ctDNA clearance was associated with an OS benefit (HR, 0.39; 95% CI, 0.19–0.73), consistent with prior studies across tumor types.

The combination was well tolerated at DCO3, with no new safety signals observed and no additional adverse events leading to treatment discontinuation of camizestrant (n = 2, 1%), consistent with previous reports. Bidard and colleagues concluded that all primary, secondary, and exploratory end points supported the benefit of the early switch to camizestrant upon ESR1 mutation emergence, ahead of disease progression. SERENA-6 was among the most anticipated breast cancer readouts at ASCO 2026, and these updated results, including the statistically significant PFS2 outcome and ctDNA clearance data, provide additional evidence supporting the early-switch treatment paradigm in ESR1-mutated ER+/HER2– advanced breast cancer.

Reference

Bidard F-C, Turner NC, et al. First-line camizestrant for emergent ESR1 mutations in advanced breast cancer: final progression-free survival 2 from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 16):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007