Biomarker-Directed Salvage Therapy

The patient experienced disease progression after 4 months on SG, with increased lymph node involvement. The shorter duration of efficacy is supported by real-world data.

Next-generation sequencing of liver biopsy tissue revealed a microsatellite stable (MSS) status, PIK3CA and HER2 mutations, and a tumor mutational burden (TMB) of 79 mut/Mb.

The patient started pembrolizumab monotherapy for TMB-high mTNBC and response is ongoing.

Whole-exome sequencing (WES) is the preferred method for detecting TMB as a predictor of immunotherapy response in breast cancer, including TNBC. TMB and PD-L1 expression are independent biomarkers in most cancers. Several panels are commercially available but only some are FDA-approved. High TMB is more common in metastatic vs primary disease (8.4% vs 2.9%) and in metastatic lobular vs ductal disease (17%; this patient vs 7.8%).

Pembrolizumab is approved for tumor-agnostic use in pretreated TMB-high (≥10 mut/Mb) metastatic disease with no satisfactory alternative therapeutic options. Use is supported by phase 2 data from the KEYNOTE-158 basket study (N=351) showing an ORR of 30%, mPFS of 3.5 months and median OS of 20.1 months across tumor types; few breast cancers were included. The TAPUR phase 2 basket study (N=28) evaluated pembrolizumab in heavily pretreated mTNBC (46%) or HR+/HER2- mBC (43%) with a median TMB of 13 mut/Mb (range, 9-37). Results showed a disease control rate of 37% with an ORR of 21%; mPFS was 10.6 weeks.