However, a different pattern was seen with tumor mutational burden (TMB), a FoundationOne panel. Patients with TMB-high tumors had a substantial gain in overall survival from atezolizumab versus chemotherapy (HR, 0.68; 95% CI, 0.51-0.90), whereas those with TMB-low tumors did not (HR, 1.00; 95% CI, 0.75-1.32).
“TMB appears to be a predictive but not a prognostic biomarker,” Dr. Powles said. “It’s not perfect. Complete and partial responses and long overall survival were seen in both arms. Nevertheless, it seems like a step in the right direction.”
Finally, with insight on the nature and relationships of the various biomarkers, the investigators assessed the combination of TMB with PD-L1, finding that atezolizumab had a marked overall survival benefit in patients with TMB-high and PD-L1–positive tumors (17.8 vs. 10.6 months; HR, 0.50; 95% CI, 0.29-0.86).
“I think by using combinations of biomarkers, first-generation and second-generation, we may actually be able to better select patients for treatment in the future,” Dr. Powles concluded.