A phase II randomized trial evaluating consolidative nivolumab in locally advanced non-small cell lung cancer post neoadjuvant chemotherapy plus nivolumab and concurrent chemoradiotherapy (GASTO-1091).

8008 Background: Enhancing clinical outcomes in resectable non-small cell lung cancer (NSCLC) has been associated with neoadjuvant or perioperative administration of nivolumab. However, the efficacy and safety of consolidation nivolumab versus observation following neoadjuvant chemotherapy plus nivolumab, hypofractionated radiotherapy and concurrent chemotherapy (hypo-CCRT) in patients with unresectable stage III NSCLC remain underexplored. Methods: Conducted as a randomized, multi-center, phase 2 trial in patients with unresectable stage IIIA-C NSCLC, this study enrolled individuals aged 18 to 75 with an ECOG performance status of 0 or 1. Neoadjuvant therapy consisted of docetaxel, cisplatin, and nivolumab (360mg every 3 weeks for 2 cycles), followed by hypo-CCRT. Patients without disease progression or G2+ pneumonitis after hypo-CCRT were randomly assigned to receive nivolumab (360 mg every 3 weeks for up to 12 months) or undergo observation. Randomization factors included age, sex, smoking history, and EGFR mutation status. The primary endpoint was progression-free survival (PFS) from randomization, with preplanned analysis results reported herein. The trial is registered with ClinicalTrials.gov, NCT04085250. Results: Between Dec 3rd, 2019, and Aug 18th, 2023, 264 patients underwent neoadjuvant therapy, 242 received hypo-CCRT, and 172 were randomly assigned to nivolumab consolidation (n = 86) or observation (n = 86) post hypo-CCRT. At the January 31, 2024, data cutoff, the median follow-up for all randomized patients was 22.8 months. Nivolumab consolidation exhibited significantly longer PFS compared to observation (median not reached vs. 12.2 months [95% CI 6.2-18.1]; hazard ratio 0.49 [95% CI 0.31-0.79], p = 0.002). The 12-month and 18-month PFS rates were 72.6% and 64.8% in the consolidation group, contrasting with 52.5% and 42.3% in the observation group. Grade 3-4 nonhematological adverse events occurred in 14.0% (37/264) during neoadjuvant therapy and hypo-CCRT. Following randomization, grade 3-5 adverse events occurred in 7.0% (6/86) with consolidation (G3 pneumonitis, 2.3%; G5 pneumonitis, 1.2%; G3 proximal bronchial tree toxicity, 3.5%) and 4.6% (4/86) with observation (G3 pneumonitis, 2.3%; G3 proximal bronchial tree toxicity, 2.3%). Conclusions: Consolidation with nivolumab after neoadjuvant chemotherapy plus nivolumab and hypo-CCRT demonstrates effectiveness and tolerability for patients with unresectable stage III NSCLC. Extended follow-up is essential for confirming these findings. Clinical trial information: NCT04085250 .