New Role of Tumor Mutation Burden as a Predictor to Chemo/Targeted Therapy in Advanced Non-Small Cell Lung Cancer

Background: Accumulating evidence illustrates greater benefit of immunotherapy in tumors with high-TMB, whereas its impact on response to targeted therapy or chemotherapy is undefined.Methods: In this retrospective study, we investigated the correlation of tumor mutation burden (TMB) and progression-free survival (PFS) of NSCLC patients who received EGFR-TKIs or Pemetrexed/Platinum as first line therapy. TMB was evaluated by targeted next generation sequencing (tNGS). Patients were divided into low(L) / intermediate(I) / high(H) TMB groups by tertiles.Results: In EGFR-mutant cohort, TMB-L patients had an massively improved PFS compared to TMB-I/H patients(P=0.006) when treated with first generation of EGFR-TKIs. In EGFR/ALK wild-type cohort who received Pemetrexed/Platinum regimen, the ORR in TMB-L group was statistically superior than that of TMB-I/H groups (P=0.037), and patients with low TMB had a numerically, but not significantly prolonged PFS (P=0.22). No difference in PFS was observed between TMB-I and TMB-H groups in two treatment arms.Conclusions: Low nonsynonymous TMB indicated a favorable PFS for EGFR-TKIs and positive response to Pemetrexed/Platinum in certain cohorts with advanced NSCLC, which could potentially identify patients more suitable for targeted therapy or chemotherapy, rather than immunotherapy.Funding Statement: This work was supported by National Natural Science Foundation of China (Grant No.81702248) and Zhejiang medical and health science and technology project (Grant No.2018KY309).Declaration of Interests: The authors have declared no conflicts of interest.Ethics Approval Statement: Study protocols were approved by the Ethical Review Community of Zhejiang Cancer Hospital. The requirement of informed consent was waived by the committee as it was a retrospective research.