PADA-1 shows clinical utility of blood ESR1 mutation monitoring
medwireNews: Women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer benefit from switching from an aromatase inhibitor (AI) to fulvestrant in palbociclib combination therapy when an ESR1 mutation is detected without disease progression, phase 3 PADA-1 trial data show.
“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,” presenter François-Clément Bidard, from Institut Curie in Paris, France, told press at the 2021 San Antonio Breast Cancer Symposium in Texas, USA.
He said: “The trial suggests a statistically and clinically significant benefit when fulvestrant is used during this very new window of opportunity.”
The multicenter study included 1017 women who were treated with an AI plus palbociclib as first-line therapy and provided blood samples for ESR1 mutation screening at baseline, 1 month and every 2 months thereafter. The women had received no prior treatment for metastatic breast cancer.
After a median 15.6 months of follow-up, 172 participants had rising ESR1 mutations but no evidence of disease progression. These women were randomly assigned to continue with standard AI plus palbociclib therapy (n=84) or to switch to fulvestrant plus palbociclib (n=88).
During a subsequent median 26.0 months of follow-up, there were 136 cases of disease progression or death among the randomized participants. Bidard reported that the risk for disease progression or death was a significant 37% lower for the women who switched to fulvestrant relative to those who stayed on standard therapy. Specifically, median progression-free survival (PFS) was 11.9 months in the fulvestrant arm and 5.7 months in the standard therapy arm.
Bidard noted that there were “no new safety signals.” The most commonly reported grade 3 or 4 adverse event (AE) was neutropenia, occurring in 36.4% of participants in the fulvestrant group and 36.9% of those in the standard therapy group and. A respective 7.9% and 7.1% needed dose reductions and one patient in the fulvestrant group discontinued therapy due to a fulvestrant-related AE.
The presenter also reported that of the 69 patients who developed disease progression following randomization to the standard therapy arm, 47 opted to cross over to fulvestrant plus palbociclib.
This group had an additional median follow-up period of 14.7 months during which there were 37 PFS events. The median second-line PFS in among these women was just 3.5 months.
This suggests that the observed clinical benefit with early fulvestrant use might “not be caught up by standard fulvestrant-based second line therapy,” and may therefore “justify the implementation of the PADA-1 treatment strategy as a valid option in routine care,” Bidard concluded.
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