Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden

Tumor mutational burden (TMB) is being explored as a predictive biomarker for immunotherapy outcomes in non-small cell lung cancer.The multinational phase 3 BFAST trial evaluated safety and efficacy of first-line targeted therapies or immunotherapy for unresectable stage IIIB or IV NSCLC in patients selected for blood-based TMB (bTMB). Cohort C of the trial included patients with bTMB ≥ 10 mut/Mb (n=471) who were randomized 1:1 to atezolizumab or platinum-based chemotherapy. The cohort did not meet the primary end point of progression-free survival in the population with bTMB ≥ 16. A higher percentage of patients with atezolizumab versus chemotherapy had long-term survival. Adverse events leading to withdrawal occurred in 10% of patients in the atezolizumab group and in 20% of patients in the chemotherapy group. The authors conclude that additional exploration of bTMB to identify optimal cutoffs is warranted.