...we conducted B-F1RST (NCT02848651), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy in locally advanced or metastatic stage IIIB–IVB non-small cell lung cancer (n = 152)....Median OS was 23.9 months in the bTMB ≥ 16 group versus 13.4 months in the bTMB < 16 group (HR = 0.66, 90% CI: 0.40, 1.10, P = 0.18; Fig. 2b)….In a secondary biomarker analysis, ORR in the bTMB ≥ 16 versus bTMB < 16 subgroups was 35.7% (95% CI: 19.2, 55.5) versus 5.5% (95% CI: 2.2, 12.2) (P < 0.0001). ORR (95% CI) in the bTMB ≥ 10 versus bTMB < 10 groups was 20.4% (10.5, 33.7) versus 7.1% (2.9, 15.3). ORR (95% CI) for bTMB:≥ 20 versus bTMB < 20 was 47.4% (25.2, 69.1) versus 6.0% (2.6, 12.2).

This observational retrospective study involved 73 patients with advanced NSCLC who received either anti-PD-1 (pembrolizumab, nivolumab, or camrelizumab) or anti-PD-L1 (atezolizumab) therapy….Our results showed that the variables of male sex, smoking history, and high TMB were associated with a significantly longer PFS....Patients with high TMB and low TMB had an mPFS of 3.7 and 2.1 months (log-rank P=0.004), respectively....In univariate analysis of PFS, TMB was found to be a significant determinant of PFS (HR, 0.46; 95% CI, 0.23–0.92; P=0.027)....In multivariable analysis, TMB was identified as an independent determinant factor of PFS (HR, 0.41; 95% CI, 0.23–0.73; P=0.002)...

Significantly higher objective response rate (ORR) and DCB were observed in high abTMB patients than low abTMB patients receiving atezolizumab (20.5% vs. 11.0% for ORR, P=0.020; 40.8% vs. 23.8% for DCB, P<0.001). The median PFS (4.2 months vs. 2.4 months; adjusted hazard ratio [HR] for disease progression or death, 0.730; 95% CI, 0.593 to 0.900; P=0.003) and OS (15.9 months vs. 9.5 months; adjusted HR for death, 0.646; 95% CI, 0.508 to 0.822; P<0.001) of patients with high abTMB were significantly longer than those of patients with low abTMB in the atezolizumab arm.