Adjuvant Durvalumab in Completely Resected Early-Stage Non–Small Cell Lung Cancer

PURPOSE Adjuvant immunotherapy improved patient outcomes in two trials in completely resected non–small cell lung cancer (NSCLC), but with conflicting primary end point results. The Canadian Cancer Trials Group BR.31 trial evaluated adjuvant durvalumab in completely resected early-stage NSCLC. METHODS Following resection of stage IB (≥4 cm) to IIIA NSCLC (American Joint Committee on Cancer 7th Edition) and optional adjuvant chemotherapy, patients were randomly assigned 2:1 to durvalumab 20 mg/kg or placebo 20 mg/kg once every 4 weeks for 12 cycles. Random assignment was stratified by stage, extent of nodal dissection, tumor cell (TC) PD-L1 expression, adjuvant chemotherapy use, and center. The primary end point was investigator-assessed disease-free survival (DFS). Secondary outcomes included overall survival (OS), adverse events, and quality of life. The primary analysis was in the subgroup with cancers that had a PD-L1 TC expression ≥25%, no common activating EGFR mutations ( EGFR –), and no ALK gene rearrangements ( ALK –). Secondary analyses in hierarchical order included DFS in the subgroup whose tumors were EGFR–/ALK– with PD-L1 TC ≥1%, followed by all patients whose tumors were EGFR–/ALK–, followed by OS in the same primary and secondary subgroups in the same hierarchical order. RESULTS Of 1,415 patients randomly assigned, 1,219 (86%) had EGFR–/ALK– tumors: 815 randomly assigned to durvalumab and 404 to placebo. With a median follow-up of 60 months, there were no differences in DFS between patients assigned durvalumab (316) versus placebo (161) in the primary population (stratified hazard ratio [HR], 0.93 [95% CI, 0.71 to 1.25]; P = .64) or in the secondary populations. Grade 3 to 4 adverse events were higher in durvalumab-treated patients (D = 26% v P = 20%). CONCLUSION Adjuvant durvalumab following complete resection was not associated with improvement in DFS compared with placebo in EGFR –/ ALK – NSCLC, regardless of PD-L1 status.