Breast-cancer patients with estrogen-receptor mutation may benefit from early treatment change

Reuters Health - 13/12/2021 - Women with breast cancer taking an aromatase inhibitor (AI) plus palbociclib with evidence of a rising ESR1 mutation in blood doubled their progression-free survival after switching to fulvestrant plus palbociclib in the phase 3 PADA-1 trial.

Breast tumors can become resistant to AI therapy by mutating ESR1, the gene that encodes estrogen receptor-alpha.

"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," Dr. Francois-Clement Bidard of Institut Curie and Paris-Saclay University, in France, said in a news release from the San Antonio Breast Cancer Symposium, where he presented the research.

"The trial suggests a statistically and clinically significant benefit when fulvestrant is used during this very new window of opportunity," he added.

The PADA-1 trial recruited women with hormone-receptor-positive, HER2-negative metastatic breast cancer undergoing first-line treatment with an AI plus palbociclib. They were screened for ESR1 mutations every two months.

"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," Dr. Bidard said in the release.

A total of 172 women with rising ESR1 mutations and no concurrent disease progression were randomly assigned to continue with AI plus palbociclib therapy (84 patients) or switch to fulvestrant plus palbociclib (88 patients).

After a median of 26 months, median progression-free survival of patients who switched to fulvestrant was over twice as long as those who remained on an AI (11.9 months vs. 5.7 months; hazard ratio, 0.63; P=0.007).

Forty-seven patients who progressed after continuing AI therapy treatment crossed over to fulvestrant. With median follow up of 14.7 months, median progression-free survival was 3.5 months in this group.

The results highlight the importance of early detection of ESR1 mutations and switch to fulvestrant, the researchers say.

"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. 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," Dr. Bidard said in the release.

"The observed clinical benefit might be underpinned by a lower burden of ESR1 mutation tumor cells at the initiation of fulvestrant," Dr. Bidard told a press briefing.

This study was funded by Pfizer. Dr. Bidard holds a patent for the ESR1 droplet digital PCR assay used in the study and has financial ties to Pfizer and other drugmakers.

SOURCE: https://www.sabcs.org/ San Antonio Breast Cancer Symposium, held December 7-10, 2021.

By Megan Brooks



Posted on 13 December 202114 December 2021