BRCA/PALB2 Mutations Cut Real-World PFS to 11 mo on First-Line CDK4/6i in HR+/HER2− mBC

Using France’s ESME registry, investigators retrospectively analyzed 4820 women with HR+/HER2− metastatic breast cancer who initiated first-line CDK4/6 inhibition plus endocrine therapy between 2013-2023 (palbociclib 74%, ribociclib 17%, abemaciclib 13%). Median PFS was 11.2 m for the 90 patients harboring pathogenic BRCA1/2 or PALB2 variants versus 15.7 m in 523 tested wild-type and 18.9 m in 4207 untested patients (adjusted HR 1.48, p = 0.003); OS was ~50 m in both mutation-positive and wild-type groups. By contrast, pivotal randomized trials of palbociclib (PALOMA-2) and abemaciclib (MONARCH 3) report PFS 24.8 m and 29 m, respectively, in unselected HR+/HER2− disease, highlighting a sizeable efficacy gap for germline DDR-mutated tumors.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P2-09-23/752366/Abstract-P2-09-23-Differential-outcomes-of