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SAN ANTONIO -- In a novel study in metastatic breast cancer, hormonal therapy was switched when blood test results showed a biomarker for resistance, and the change appeared to extend progression-free survival (PFS), a researcher reported.

For patients on aromatase inhibitor (AI) therapy, median PFS was 11.9 months for the group that switched to fulvestrant (Faslodex) when the estrogen receptor gene mutation ESR1 was detected in the blood, as compared with 5.7 months for those who continued on AI treatment (hazard ratio 0.63, 95% CI 0.45-0.88, P=0.005), said François-Clément Bidard, MD, PhD, of Institut Curie/Université Paris-Saclay.

All patients in the so-called (Palbociclib and Circulating Tumor DNA for ESR1 Mutation Detection) study were also treated with palbociclib (Ibrance) as part of their first-line treatment regimen, Bidard said in an oral presentation at the .

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

"That benefit might not catch up when you wait," he continued, "which might justify the adoption of the PADA-1 treatment strategy as a valid option in routine care."

The idea behind the study was based on knowledge that an ESR1 mutation is considered an indication that AIs are less likely to be effective. "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," Bidard explained.

"While the concept of treating on the basis of blood markers of resistance has been around a while, actually being able to do such a trial is remarkable," Minetta Liu, MD, of the Mayo Clinic in Rochester, Minnesota, told 名媛直播.

"These findings support serial circulating tumor DNA monitoring as a means to identify and react to treatment resistance as soon as possible," she added. "Whether this strategy translates into a meaningful survival benefit remains to be demonstrated. The potential to avoid disease-related symptoms with an earlier change in therapy needs to be explored."

PADA-1 enrolled 1,017 patients with metastatic breast cancer who were initially treated with AIs and palbociclib as first-line therapy. By monitoring for the ESR1 mutation, the researchers eventually identified 172 patients with the mutation, and those patients were randomized to continue on the same AI regimen or switch from the daily AI to monthly injectable fulvestrant (84 and 88 patients, respectively). At the point of the switch, none of the patients had evidence of progressive disease.

During the study, median time to emergence of the ESR1 mutation was about 14 months, Bidard reported. When progression occurred, patients on the AI regimen were then allowed to switch to fulvestrant; median second-line PFS in that crossover group was 3.5 months.

Liu noted that given the difference between oral therapy with AIs and regular intramuscular injections with fulvestrant, research is also needed about how the switch in therapy might affect quality of life.

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