1026P Treatment switching adjustment of overall survival in the CheckMate 227 clinical trial of nivolumab plus ipilimumab versus chemotherapy in first-line treatment of patients with advanced non-small cell lung cancer

Abstract

CheckMate 227 is a phase III clinical trial designed to evaluate the efficacy of nivolumab plus ipilimumab vs platinum doublet chemotherapy in patients with stage IV or recurrent non-small cell lung cancer (NSCLC) previously untreated for advanced disease. Some patients in the chemotherapy arm subsequently switched to an immunotherapy due to toxicity or progressive disease. We update overall survival estimates by adjusting for potential biases introduced by treatment switching from chemotherapy to subsequent immunotherapy. The Inverse Probability of Censoring Weights (IPCW) method that adjusts the treatment effect estimates in the presence of informative censoring was applied to adjust OS for treatment switching in the ITT population as a post hoc analysis based on 3-year follow up data. The IPCW method, being well recognized by health authorities, was considered as the base case. Other treatment switching adjustment methods were explored as sensitivity analysis. Exploratory analyses were also conducted in select subgroups. In part 1 of the trial, a total of 1166 patients (583 each arm) were included in the analysis. 235 (40.3%) patients in the chemotherapy arm switched to an immunotherapy. Median OS was 17.1 months (95% CI: 15.5 to 20.0) for the nivolumab plus ipilimumab arm and 14.0 months (95% CI: 12.6-15.4 months) for the chemotherapy arm. After adjustment for treatment switching, the median OS for the chemotherapy arm was 10.8 months (95% CI: 9.2 -12.8). The hazard ratio (HR) of nivolumab plus ipilimumab versus chemotherapy was 0.74 (95% CI: 0.65 to 0.85), which after adjustment reduced to 0.62 (95% CI: 0.53 to 0.73). Based on 3-year follow up data from CheckMate 227, adjusting for treatment switching biases in the chemotherapy arm resulted in a numerically greater estimated relative OS benefit with nivolumab plus ipilimumab over chemotherapy in previously untreated patients, with advanced NSCLC without EGFR/ALK aberrations than in the unadjusted analysis.