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William J. Gradishar, MD, FACP, FASCO


Does Pairing Fulvestrant and Palbociclib Improve Clinical and Kinetic Outcomes in ESR1-Mutated Breast Cancer?

By: Kayci Reyer
Posted: Tuesday, July 18, 2023

According to findings from the PADA-1 trial, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1002), administering the CDK4/6 inhibitor palbociclib in conjunction with the estrogen receptor antagonist fulvestrant versus an aromatase inhibitor resulted in improved outcomes for patients with estrogen receptor–positive, HER2-negative metastatic breast cancer that harbors a rising ESR1 mutation in the blood. Results from circulating tumor DNA analyses supported the observed clinical benefit.

ESR1 mutation type and clonality did not impact the benefit of the treatment switch,” noted Luc Cabel, MD, of the Curie Institute, St. Cloud, France, and colleagues.

The study included patients who received a first-line aromatase inhibitor plus palbociclib before being randomly assigned to either remain on the treatment or to replace the regimen with fulvestrant plus palbociclib. A total of 172 patients with a rising ESR1 mutation in the blood without synchronous disease progression were enrolled. Among them, the median mutant allelic frequency of mutated ESR1 was 0.8%, and the median copy number/mL of plasma was 14 on a rising sample. At a repeat blood sample held at randomization, 75 patients (46.6%) had no detectable ESR1 mutation.

Patients in the fulvestrant arm experienced a higher rate of ESR1 mutation clearance (70.9% vs. 32.8%) at a 2-month follow-up as well as a longer median length of clearance (7.3 months vs. 1.9 months). At the time of disease progression, 83% and 73% of patients in the aromatase inhibitor and fulvestrant arms, respectively, harbored detectable ESR1 mutation. Although it did not seem to influence survival and clinical outcomes, Y537S was noted to be the most commonly occurring mutation type among 95 evaluable patients.

Disclosure: Dr. Cabel reported no conflicts of interest. For full disclosures of the other study authors, visit

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