Dr Hurvitz on Updated PFS Data From the SERENA-6 Trial in Breast Cancer

“There were some interesting discussions surrounding the use of PFS2 at [the 2026 ASCO Annual Meeting] and the validity of using that as a surrogate marker of long-term benefit from a therapy.”

Sara A. Hurvitz, MD, FACP, senior vice president and director of the Clinical Research Division, the Smith Family Endowed Chair in Women’s Health, and an affiliate investigator in the Translational Science and Therapeutics Division at the Fred Hutchinson Cancer Center; as well as head of the Division of Hematology and Oncology at the University of Washington School of Medicine, discussed updated findings from the phase 3 SERENA-6 trial (NCT04964934) evaluating a switch to camizestrant plus a CDK4/6 inhibitor upon the detection of an emergent ESR1 mutation in circulating tumor DNA (ctDNA) vs continuation of an aromatase inhibitor plus a CDK4/6 inhibitor in patients with hormone receptor–positive, HER2-negative metastatic breast cancer.

With updated follow-up, the switch to camizestrant conferred a 7.6-month improvement in median progression-free survival (PFS), Hurvitz reported. The median PFS was 16.8 months (95% CI, 14.7-19.4) with camizestrant (n = 157) compared with 9.2 months (95% CI, 7.2-9.7) in patients who continued the aromatase inhibitor plus a CDK4/6 inhibitor (n = 158), a difference that reached statistical significance at a median follow-up of 23.5 months, she noted (HR, 0.45; 95% CI, 0.34-0.59; nominal P < .00001).

Since the study was not powered to evaluate overall survival as an end point, the investigators followed time to second progression (PFS2) to assess whether the benefit derived from switching to camizestrant upon ctDNA-detected ESR1 positivity proved durable, Hurvitz explained. She reported that the median PFS2 outcomes favored the camizestrant arm by 6.6 months, at 25.7 months (95% CI, 20.4-30.3) vs 19.1 months (95% CI, 16.8-21.0) in the control arm; this difference was also statistically significant (HR, 0.63; 95% CI, 0.46-0.86; nominal P < .00373).

However, Hurvitz emphasized that the use of PFS2 as an end point in this trial generated notable discussion at the 2026 ASCO Annual Meeting, particularly regarding its validity as a surrogate marker for long-term therapeutic benefit. She further highlighted a discussion referencing data from the phase 2 SERENA-2 study (NCT04214288) of camizestrant monotherapy in patients with estrogen receptor–positive, HER2-negative advanced breast cancer that further questioned whether PFS2 findings should influence the decision to switch to this agent early upon ctDNA progression.

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