The phase 3 PADA-1 trial demonstrates for the first time that changing hormone therapy following early detection of ESR1 mutations in plasma in some patients with hormone receptor-positive breast cancer treated with an aromatase inhibitor plus palbociclib (Ibrance) can delay the onset of cancer resistance to standard therapy.
The results were presented at San Antonio Breast Cancer Symposium 2021 (SABCS) by the study coordinator Prof François-Clément Bidard (Curie Institute). After a median follow-up of 26 months, the median progression-free survival significantly doubled (11.9 months vs 5.7 months) when treatment switched to fulvestrant (Faslodex) plus palbociclib before a detectable clinical disease progression.
Thanks to the commitment of 83 French centers, the PADA-1 trial recruited 1,017 patients. Patients with metastatic ERα-positive breast cancer that lacked expression of the growth factor receptor HER2, were treated in a first-line setting with an aromatase inhibitor plus palbociclib. The patients provided blood samples for ESR1 mutation screening every two months, by ddPCR. Two molecular platforms were involved to perform these tests and deliver the results in a short time : Curie Institute, Paris and IUCT-Oncople, Toulouse.
At rising ctDNA, patients who did not experienced a concurrent disease progression could be randomized to continuing palbociclib and their aromatase inhibitor or switch to palbociclib + fulvestrant. 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 (N= 219 pts) or concurrent (N= 60 pts) with disease progression. Patients who progressed after continuing aromatase inhibitor treatment were given the option to cross over to the fulvestrant arm of the study.
This French Breast Cancer Intergroup UNICANCER (UCBG) study, conducted in partnership with the GINECO intergroup, demonstrates the ability of these INCa labelized intergroups to conduct large-scale studies with complex logistics. PADA-1 received an institutional support from Pfizer.
Future directions include learning more about the clinical features of ESR1-mutated tumors and trying to predict which patients will develop mutations.