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William J. Gradishar, MD, FACP, FASCO


Do Patients With ESR1-Mutated Breast Cancer Benefit From Early Switch to Palbociclib Plus Fulvestrant?

By: Julia Fiederlein
Posted: Tuesday, February 1, 2022

Using combination therapy with the CDK4/6 inhibitor palbociclib plus fulvestrant to target blood ESR1 mutation–associated resistance seemed to be feasible in patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were treated with palbociclib plus an aromatase inhibitor, according to François-Clément Bidard, MD, PhD, of Paris-Saclay University, France, and colleagues. The results of the multicenter phase III PADA-1 trial, which were presented during the 2021 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-05), also revealed that changing the endocrine partner of palbociclib doubled the median duration of progression-free survival.

“Fulvestrant…provides a limited progression-free survival benefit when used as a second-line therapy,” commented Dr. Bidard in an SABCS press release. “Our goal was to track the emergence of ESR1 mutations in patients’ blood during first-line therapy and act on them as soon as they appeared, before they led to an actual clinical progression of the disease.”

A total of 1,017 patients received first-line treatment with palbociclib plus an aromatase inhibitor; they provided blood samples for screening every 2 months. After a median of 15.6 months, patients with a rising ESR1 mutation in the blood and no synchronous disease progression were randomly assigned to continue this therapy (n = 84) or switch to palbociclib plus fulvestrant (n = 88). A subgroup of patients who experienced disease progression after continuing therapy with an aromatase inhibitor crossed over to fulvestrant (n = 47).

Among the randomly assigned patients, a total of 136 progression-free survival events were observed after a median follow-up of 26 months. The median durations of progression-free survival were 5.7 and 11.9 months with an aromatase inhibitor and fulvestrant, respectively (P = .007). At a median follow-up of 14.7 months, the median duration of the second progression-free survival was 3.5 months in patients who crossed over to fulvestrant; a total of 37 progression-free survival events were observed.

Disclosure: For full disclosures of the study authors, visit

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