Pembrolizumab (PD-1) KEYNOTE-522 neoadjuvant regimen: gBRCA+ trends to higher pCR and 2-year RFS in early TNBC

Pembrolizumab, an anti–PD-1 antibody, combined with platinum/taxane → anthracycline/cyclophosphamide chemotherapy per the KEYNOTE-522 regimen (NCT03036488) was evaluated in a retrospective single-center real-world cohort of stage II–III TNBC treated January 2021–December 2023 with documented germline BRCA status (n=54; BRCA+ n=11, BRCA− n=43). pCR (ypT0/is ypN0) was 60% overall (31/52 evaluable) and numerically higher with BRCA+ vs BRCA− (73% [8/11] vs 56% [23/41]; p=0.49); at median 25-month follow-up, 2-year RFS was 100% vs 75.4% (p=0.068) and 2-year OS 100% vs 88% (p=0.272). In BRCA− patients, pCR strongly stratified outcomes (2-year RFS 100% with pCR vs 45.5% without; p=0.00004; 2-year OS 100% vs 72.7%; p=0.018)—directionally consistent with the randomized KEYNOTE-522 benchmark pCR ≈64.8% with pembrolizumab vs 51.2% with chemo alone, and with residual-disease escalation norms like adjuvant capecitabine (CREATE-X) and gBRCA-directed adjuvant olaparib (OlympiA) where eligible.