Investigating the various predictive values of TP53 mutations for response to immune checkpoint inhibitors (ICIs) in different solid tumors.

Abstract

e14581 Background: TP53, a well-known tumor suppressor gene that encodes p53.The mutations of TP53 have been shown to be associated with higher tumor mutation burden (TMB). And patients with TP53 mutations are more likely to benefit from ICIs therapy. Previous studies have shown that TMB has divergent predictive value for response to ICIs therapy in different cancer types. We hypothesized that the associations between TP53 mutations and ICIs efficacy are also varied in different solid tumors. Therefore, we explored the prediction values of TP53 mutations in some cancer types. Methods: The ICIs treatment cohort from the Memorial Sloan Kettering Cancer Center (MSKCC) was selected to analyze the association of TP53 mutations with ICIs efficacy. The patients were classified into two groups: TP53 mutation (Mut) and wildtype (WT). Overall survival (OS) after ICIs therapy was estimated with the Kaplan-Meier method. Results: In MSKCC pan-cancer dataset, patients with TP53 mutations had significantly shorter median OS after ICIs therapy (14.00 vs 23.00 months, P < 0.0001), indicating that TP53 mutations were associated with worse immunotherapy outcome. Then we analyzed the predictive roles in each cancer type. Notably, we found the associations of TP53 mutations with longer median OS in bladder cancer (27.00 vs 14.00 months, P = 0.0359). However, the associations between TP53 mutations and ICIs efficacy were not observed in breast cancer, esophagogastric cancer, glioma, head and neck cancer, melanoma, non-small cell lung cancer and renal cell carcinoma. We found the associations of TP53 mutations with shorter median OS in colorectal cancer (13.00 vs 34.00 months, P = 0.0368). Furthermore, the data showed that the median TMB was significantly lower in the Mut group for colorectal cancer (17.63 vs 35.98 muts/Mb, P = 0.0086) and higher in the Mut group for bladder cancer (14.25 vs 10.81 muts/Mb, P = 0.1588). Conclusions: Although TP53 mutations were associated with better ICIs efficacy in previous studies, the prolonged OS was only found in the Mut group for bladder cancer. Although TP53 mutations were associated with worse ICIs efficacy for all the enrolled patients, the poor outcome was only found in the Mut group for colorectal cancer. These data suggested that TP53 mutations may be a useful predictor for ICIs efficacy in these two types of cancer.