46: Cross-trial propensity score weighted analysis of nivolumab plus ipilimumab versus nivolumab monotherapy for patients with untreated advanced renal cell carcinoma

Background: Nivolumab plus ipilimumab (NIVO+IPI) is an established first-line combination treatment for intermediate- or poor-risk (int/poor-risk) patients with advanced renal cell carcinoma (aRCC). Recent results from part A of the single-arm, phase 2 HCRN GU16-260 trial indicate that NIVO monotherapy has activity in untreated aRCC. In the absence of head-to-head data, we describe a cross-trial propensity score (PS) weighted analysis comparing efficacy of NIVO+IPI versus NIVO in patients with untreated aRCC.

Methods: Data were derived from patients randomized to NIVO+IPI in the CheckMate 214 trial (minimum 5-year follow-up) and NIVO-treated patients in part A of HCRN GU16-260 (minimum 3-year follow-up). PS weights were computed for each patient using a logistic regression model with treatment group (NIVO+IPI or NIVO) as the dependent variable and a set of clinically meaningful baseline covariates as independent predictors. Investigator-assessed objective response rate (ORR) and progression-free survival (PFS) were compared between the 2 treatment groups in IMDC any-risk and IMDC int/poor-risk populations.

Results: In both IMDC populations, all notable baseline covariate imbalances between treatment groups were balanced by PS weighting. In the unweighted analysis, ORR and PFS benefits of NIVO+IPI over NIVO monotherapy were seen only for the IMDC int/poor-risk population (Table). However, after applying the PS weights and adjusting for confounding effects to reduce potential bias in the estimated treatment benefits of NIVO+IPI over NIVO monotherapy, ORRs were numerically higher and PFS was longer with NIVO+IPI in both IMDC populations.

Conclusions: This exploratory cross-trial PS-weighted analysis suggests that NIVO+IPI provides efficacy benefits over NIVO monotherapy in both IMDC any-risk and IMDC int/poor-risk populations with untreated aRCC. The phase 3b CheckMate 8Y8 trial (NCT03873402) directly comparing NIVO+IPI and NIVO in int/poor-risk patients with untreated aRCC is ongoing.