转移性三阴性乳腺癌患者接受帕博利珠单抗或化疗后潜在生物标志物与临床结局的关联

In the randomized, phase 3 KEYNOTE-119 study, overall survival (OS) was not significantly improved with pembrolizumab 200 mg Q3W versus investigator's choice of chemotherapy in participants with previously treated metastatic TNBC. In this exploratory analysis, we evaluated associations of tumor-infiltrating lymphocytes (TILs), T-cell inflamed gene expression profile (Tcell inf GEP), BRCA1/BRCA2 mutation (BRCAm) status, homologous recombination deficiency (HRD) status, and tumor mutational burden (TMB) with clinical outcomes.

TIL level was associated with improved objective response rate (ORR), progression-free survival (PFS), and OS with pembrolizumab but not with chemotherapy or after adjusting for Tcell inf GEP. Associations were also identified between Tcell inf GEP and improved ORR, PFS, and OS with pembrolizumab. Participants with TMB 10 mut/Mb showed a trend toward increased benefit with pembrolizumab versus chemotherapy. No association was seen between BRCAm/HRD status and treatment response.

These findings suggest a positive association between TILs, Tcell inf GEP, and TMB with clinical outcomes in patients with metastatic TNBC receiving pembrolizumab. ClinicalTrials. gov Identifier: NCT02555657 (date of registration: September 18, 2015).