Abstract 104P
Background
Immune checkpoint inhibitors (ICIs), as a revolutionary new immunotherapy therapy, can improve the survival of cancer patients. Nevertheless, ICIs are only effective for some patients. Therefore, there is an urgent need to explore biomarkers that can predict prognosis in cancer patients treated with ICIs. Neurotrophin tyrosine kinase receptor 3 (NTRK3) acts as a tumor suppressor or oncogene in the development of various cancers. However, the efficacy of NTRK3 mutation in immunotherapy for patients with cancer is unknown. Herein, we aimed to analyze the association between NTRK3 mutation and the efficacy of ICIs.
Methods
We screened 1661 patients with advanced cancer in the MSKCC cohort who had complete information, received at least one dose of ICI, and whose tumors underwent next-generation sequencing (NGS). The patients were divided into NTRK3 mutant type (NTRK3-MT) group and NRTK3 wild type (NTRK3-WT) group according to NTRK3 mutation status. We analyzed the differences in overall survival (OS) and TMB between the two groups. Pooled hazard ratios (HR) and 95% confidence intervals (CI) for OS were calculated by Cox regression models, and P values were calculated by Wilcoxon's sign test for TMB.
Results
Among 1661 advanced cancer patients, 75 (4.5%) NTRK3-MT and 1586 (95.5%) NTRK3-WT. NTRK3-MT group had significantly longer OS (p=7.0e-5; HR=0.42; 95% CI: 0.27-0.65) and higher TMB (p<2.2e-16). In total 1661 patients, 350 (21.1%) were non-small cell lung cancer (NSCLC), including 20 (5.7%) NTRK3-MT and 330 (94.8%) NTRK3-WT. NTRK3-MT group also had significantly longer OS (p=0.01; HR=0.36; 95% CI: 0.16-0.81) and higher TMB(p=1.1e-5) in NSCLC. Moreover, the 1661 patients were further divided into 4 groups according to NTRK3 status and TMB (TMB-H, TMB top 25%; TMB-L, other TMB) and found that TMB-H_NTRK3-MT group had the best OS (p=3.9e-12; HR=0.22; 95% CI: 0.94-4.62). The same outcome trends were reflected in the NSCLC cohort (p=0.01; HR=0.22; 95% CI: 0.70-4.63).
Conclusions
Our study founded that patients with cancer harboring NTRK3 mutation tended to have higher TMB and longer OS for the first time. In the future, relevant prospective clinical trials need to be designed to verify this conclusion.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.