Abstract
Background: NICOLAS is the first completed single-arm phase II trial in stage III NSCLC examining hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemo-radiotherapy. The safety endpoint was reported earlier; here we present the efficacy results.
Methods: Stage IIIA/B unresectable treatment-naive NSCLC patients received 3 cycles of platinum-based chemotherapy and concurrent radiotherapy (66Gy/33fractions), along with nivolumab (360mg/Q3W). Nivolumab was continued as monotherapy consolidation for a maximum of one year (480mg/Q4W). The primary endpoint was 1-year PFS, with a target improvement compared to historical data of at least 15%, from 45% to 60%. For testing this efficacy hypothesis, a sample size of 74 evaluable patients provides power 83%, at 1-sided alpha 5%.
Findings: 79 patients were enrolled with median follow-up 21.0 months (m) (Interquartile Range:15.8m-25.8m) for the primary PFS analysis. 35.4% of patients had stage IIIA and 63.3% stage IIIB. The 1-year PFS was 53.7% (95%CI[42.0%-64.0%]), the median PFS 12.7m (95%CI[10.1m-22.8m]). Since among the 74 first evaluable patients, 37 PFS events occurred in the first year post-treatment, a 1-year PFS rate of ≤45% could not be rejected (p-value=0.23). At an extended follow-up (32.6m median), 37 deaths have been recorded, with a median OS 38.8m(95%CI[26.8m-Not Estimable]) and a 2-year OS rate of 63.7% (95%CI[51.9%-73.4%]). The OS of stage IIIA patients was found to be significantly higher than stage IIIB patients, with 2-year OS 81% and 56% respectively (p=0.037).
Conclusion: PFS and OS are arithmetically higher to studies in the same population, however, based on the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is ≤45%.
Peters, S