Nicholas C. Turner, MD, PhD, on ER-Positive, HER2-Negative Advanced Breast Cancer: persevERA BC Trial
ASCO 2026
Nicholas C. Turner, MD, PhD, of the Royal Marsden Hospital, Institute of Cancer Research, discusses results from the primary analysis of the persevERA BC trial, which investigated giredestrant plus palbociclib vs letrozole plus palbociclib as first-line therapy in patients with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (Abstract LBA1006).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Giredestrant is being designed as an oral SERD and complete ER antagonist. We've already seen two positive phase III trials with giredestrant, evERA in combination with everolimus in the metastatic setting and lidERA as a single agent better than standard endocrine therapy in the adjuvant setting. So persevERA is the third phase III study to report with giredestrant, and this looked at the first-line setting in patients with metastatic ER-positive, HER2-negative advanced breast cancer. Standard of care here is, of course, an aromatase inhibitor and a CDK4/6 inhibitor. And persevERA was designed to assess whether switching from an AI to giredestrant could improve PFS. So the study randomized just under 1,000 patients between letrozole and palbociclib and giredestrant and palbociclib in a double-blind fashion. And the primary endpoint was investigator-assessed PFS. Overall, the study was negative. There was no statistically significant improvement in PFS. The hazard ratio was 0.89, but there clearly appeared to be a numerical improvement of PFS with giredestrant. The curves, interestingly, appeared to be overlapping for the first 12 months, perhaps suggesting that early recurrences are not driven by ER; they're driven by other mechanisms of resistance, and then the curves appear to separate. Potentially, giredestrant here is active because these later recurrences are driven, it's preventing the emergence of ESR1 mutations. And so, overall, the study does confirm the high activity of giredestrant, but not better than an aromatase inhibitor in this study combined with palbociclib.
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