Consolidative nivolumab versus observation in unresectable stage III non-small cell lung cancer patients following neoadjuvant nivolumab plus chemotherapy and concurrent chemoradiotherapy (CA209-7AL): a randomized clinical trial.

CA209-7AL is a randomized, multicenter, phase 2 trial evaluating the efficacy and safety of consolidative nivolumab (NIVO) versus observation following neoadjuvant NIVO plus chemotherapy and concurrent chemoradiotherapy (CCRT) for unresectable stage III NSCLC. Patients received 2 cycles of neoadjuvant chemo-NIVO therapy (docetaxel + cisplatin + NIVO) and CCRT (total dose 54-64 Gy). Post-CCRT, eligible patients were randomized 1:1 to receive consolidative NIVO (360 mg every 3 weeks for up to 12 months) or observation. The primary endpoint was progression-free survival (PFS) from randomization. Between December 3rd, 2019, and August 18th, 2023, 264 patients were enrolled, and 172 were randomized to NIVO consolidation (n = 86) or observation (n = 86). With a median follow-up of 22·8 months, NIVO consolidation resulted in significantly longer PFS than did observation (median not reached vs. 12.2 months [95% CI 10.2-20.8]; stratified hazard ratio 0·49 [95% CI 0.30-0.79], p = 0.003). NIVO consolidation also demonstrated superior PFS compared with a parallel real-world study, where patients received CCRT followed by consolidative immunotherapy (median PFS: 15.7 months [95% CI 11.9-NA]). Grade 3 or 4 toxicities occurred in 9.3% of patients in the consolidation group versus 4·6% in the observation group, with similar rates of pneumonitis (2.3% each) and proximal bronchial tree toxicity (3.5% vs. 2.3%). Treatment-related death occurred in 1 (1.2%) patient in the consolidation group because of pneumonitis. Patients with a high TMB had a longer PFS with consolidation (NR vs. 15.2 months, p = 0.042). Consolidative NIVO following neoadjuvant NIVO plus chemotherapy and CCRT demonstrated effectiveness and tolerability for patients with unresectable stage III NSCLC (ClinicalTrials.gov NCT04085250).