Nivolumab plus chemoradiotherapy followed by nivolumab with or without ipilimumab for untreated locally advanced stage III NSCLC: a randomized phase 3 trial.

Over 50% of persons with unresectable stage III non-small cell lung cancer (NSCLC) treated with standard-of-care concurrent chemoradiotherapy (CCRT) and durvalumab consolidation progress or die within 18 months. Here adults with untreated, unresectable stage III NSCLC were randomized to nivolumab plus CCRT followed by consolidation with nivolumab plus ipilimumab (arm A) or nivolumab alone (arm B) or CCRT followed by consolidation with durvalumab (arm C). The primary endpoint was progression-free survival (PFS) in arm A versus arm C and secondary endpoints included overall survival (OS), PFS in arm B versus arm C, response rates and safety. At a median follow-up of 30.5 months, there was no statistically significant difference in the primary endpoint of PFS in the nivolumab plus ipilimumab arm versus durvalumab arm (hazard ratio (HR): 0.95, 96% confidence interval (CI): 0.77-1.19; P = 0.65). Descriptive OS analysis showed no improvement (HR: 1.12, 95% CI: 0.87-1.43). Nivolumab alone did not improve PFS or OS versus durvalumab (PFS, HR: 0.84, 95% CI: 0.69-1.04; OS, HR: 0.97, 95% CI: 0.76-1.24). Nivolumab plus ipilimumab and nivolumab alone plus CCRT resulted in increased pneumonitis. These results emphasize the need for novel efficacious treatments for these individuals. (ClinicalTrials.gov: NCT04026412 ).