Breast Cancer Patients with Estrogen Receptor Mutations May Benefit from Early Switch to Fulvestrant/Palbociclib

In In The News by Barbara Jacoby


Among patients with hormone receptor-positive breast cancer treated with an aromatase inhibitor plus palbociclib, those who displayed a rising ESR1 mutation detected in their blood before disease progression doubled their median progression-free survival following a switch to fulvestrant plus palbociclib, according to results from the phase III PADA-1 clinical trial presented during Thursday’s General Session at SABCS 2021.

“PADA-1 is the first trial to demonstrate that, in most patients, resistance-associated mutations in the estrogen receptor gene can be detected and targeted before tumor progression,” said presenter François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and Paris-Saclay University in France. “The trial suggests a statistically and clinically significant benefit when fulvestrant is used during this very new window of opportunity.”

The PADA-1 trial recruited 1,017 patients with ERα-positive breast cancer that had no overexpression of the growth factor receptor HER2, who were being treated in a first-line setting with an aromatase inhibitor plus palbociclib. The patients provided blood samples for ESR1 mutation screening every two months.

Of the recruited patients, 407 experienced disease progression in the absence of an ESR1 mutation, and a mutation was detected in 279 patients prior to (219 patients) or concurrent with (60 patients) disease progression. Only those with an identified mutation who did not experience concurrent disease progression were randomly assigned either to continuing an aromatase inhibitor plus palbociclib (84 patients) or switched to fulvestrant plus palbociclib (88 patients).

After a median follow-up of 26 months, the median progression-free survival of patients who switched to fulvestrant was over twice as long as those who remained on an aromatase inhibitor—11.9 months, compared with 5.7 months.

Patients who progressed after continuing aromatase inhibitor treatment were given the option to crossover to the fulvestrant arm of the study. Among patients in the crossover cohort, the median progression-free survival was 3.5 months. This supported previous studies showing a relatively short benefit of fulvestrant when used as a second-line therapy, Dr. Bidard said, and emphasized the importance of early detection.

“This targeted approach, after the start of the first-line endocrine therapy but before the second line, yields a statistically and clinically significant gain in progression-free survival,” he said. “That benefit might not catch up when you wait, which might justify the adoption of the PADA-1 treatment strategy as a valid option in routine care.”

Abstract: GS3-05 Fulvestrant-palbociclib vs continuing aromatase inhibitor-palbociclib upon detection of circulating ESR1 mutation in HR+ HER2-metastatic breast cancer patients: Results of PADA-1, a UCBG-GINECO randomized phase 3 trial

Click here to read the full press release from the American Association for Cancer Research (AACR).