Abstract 356: Association of LRP1B mutation with tumor mutation burden and survival in bladder cancer patients treated with immune checkpoint inhibitors

Abstract

Abstract Background: Bladder cancer is a common genitourinary malignancy worldwide. Immune checkpoint inhibitors(ICIs) including atezolizumab, pembrolizumab, nivolumab have shown durable responses and have been approved by FDA. However ICIs demonstrate antitumor effects only in a fraction of patients, and research exploring the association between gene mutation and clinical benefit is limited. Mutations of LRP1B(The low-density lipoprotein receptor-related protein 1B) are frequently seen in solid tumors and have been reported to be associated with higher tumor mutation burden(TMB) and prolonged survival in NSCLC, melanoma and liver cancer. The association between LRP1B mutation and survival in bladder cancer is unknown. Methods: The association between LRP1B mutation with TMB was analyzed in bladder cancer patients from the public immunotherapy-treated cohort published by Miao et. al as well as a clinical cohort from 3D Medicines database involving 118 Chinese patients. Wilcoxon test was used for the comparison of TMB. Overall survival(OS) and progression-free survival (PFS) analyses were conducted in the public cohort using Kaplan-Meier curves and log-rank tests. Statistical significance was set at p = 0.05. Results: 15%(5/33) bladder cancer patients in the public immunotherapy-treated cohort and 18.6% (22/118) patients in the clinical cohort harbored LRP1B mutation. LRP1B mutation is associated with higher TMB in both public cohort(p=0.028) and clinical cohort(p=0.003). Survival analysis in the public cohort demonstrated that LRP1B mutation resulted in significantly longer OS ( 16.8 vs 8.08 months; HR, 0.16; p=0.043) and a increasing trend on PFS without significant difference (15.9 vs 4.1 months; HR, 0.62; P = 0.39) in bladder cancer patients treated with ICIs. Conclusions: This study shows that LRP1B mutation is relatively common and correlated with higher TMB in bladder cancer. LRP1B mutation may serve as a predictive biomarker of ICI benefit in bladder cancer. Citation Format: Mengmei Yang, Wenzhuan Xie, Mengli Huang, Peng Wu. Association of LRP1B mutation with tumor mutation burden and survival in bladder cancer patients treated with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 356.