Optimal Cutoff Value of the Tumor Mutation Burden for Immune Checkpoint Inhibitors: A Lesson from 175 Pembrolizumab-Treated Cases Among 6403 Breast Cancer Patients

The immune checkpoint inhibitor pembrolizumab is effective for the treatment of recurrent cancer with a tumor mutation burden-high (TMB-high) status. Globally, the cutoff value of TMB-high has been set as ≥10 mut/Mb, but the optimal cutoff value of TMB for treating breast cancer (BC) with pembrolizumab has not been identified. We re-evaluated the optimal cutoff value of TMB-high status in BC by using the clinical dataset from Japan’s Center for Cancer Genomics and Advanced Therapeutics (C-CAT) profiling database. We extracted 6403 BC cases that had been enrolled from the C-CAT database of 101,231 cases of various types of cancers. Of all 6403 BC cases, 683 (10.7%) showed TMB ≥ 10 mut/Mb as TMB-high. Of the 683 TMB-high cases, 175 were administered pembrolizumab. The receiver operating characteristic curve indicated that for treating BC with pembrolizumab, a TMB ≥ 18.5 mut/Mb was an adequate cutoff regarding sensitivity and specificity. The BC patients’ overall response rate was 21.4%. The disease control rate was 42.9%. The probability of time-to-treatment failure was significantly better in the BC cases with TMB ≥ 18.5 mut/Mb versus those with TMB < 18.5 mut/Mb (p = 0.007). These findings suggested that the optimal cutoff value of the TMB for treating breast cancer with pembrolizumab might be ≥18.5 mut/Mb.