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

Abstract

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. 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 <i>EGFR</i> mutations (<i>EGFR</i>-), and no <i>ALK</i> gene rearrangements (<i>ALK</i>-). 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. Of 1,415 patients randomly assigned, 1,219 (86%) had <i>EGFR-/ALK-</i> 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]; <i>P</i> = .64) or in the secondary populations. Grade 3 to 4 adverse events were higher in durvalumab-treated patients (D = 26% <i>v</i> P = 20%). Adjuvant durvalumab following complete resection was not associated with improvement in DFS compared with placebo in <i>EGFR</i>-/<i>ALK</i>- NSCLC, regardless of PD-L1 status.