Conclusion
Our data provide insights into the relevance between TMB and targeted/chemo therapy. Higher non-synonymous TMB correlates with inferior PFS for first-generation EGFR-TKIs in EGFR-driven patients and worse response to pemetrexed/platinum regimen in EGFR/ALK wild-type patients, which has potential clinical implications for cancer treatment but needs corroboration in larger studies.
Methods
In this retrospective study, we correlated TMB with response rate and progression-free survival (PFS) of patients who received EGFR-tyrosine kinase inhibitors (TKIs) or pemetrexed/platinum as first-line therapy. Tumor mutation burden was evaluated by targeted next-generation sequencing. Patients were divided into low (L)/intermediate (I)/high (H) TMB groups by tertiles.
Results
In EGFR-mutant cohort, TMB-L patients had a massively improved PFS compared to TMB-I and TMB-H patients (16.4 vs. 9.0 vs. 7.4 months; log-rank p = 0.006) when treated with first-generation EGFR-TKIs. In EGFR/ALK wild-type cohorts who received pemetrexed/platinum regimen, the objective response rate (ORR) of TMB-L group was statistically superior than that of TMB-I and TMB-H groups (53.8% vs. 23% vs. 8.3%; log-rank p = 0.037), and patients with low TMB had a numerically but not significantly prolonged PFS (6.9 vs. 4.3 vs. 4.6 m; log-rank p = 0.22).