Presentation (CTI)

OBJECTIVES: In POD1UM-303, retifanlimab plus carboplatin-paclitaxel (CP) was compared with placebo plus CP as first-line treatment in recurrent/metastatic squamous cell anal carcinoma (SCAC). As 50% of patients receiving placebo plus CP crossed over to retifanlimab monotherapy following disease progression, overall survival (OS) estimates for the control arm were confounded. To support interpretation of within-trial crossover-adjusted OS analyses from POD1UM-303, a matching-adjusted indirect comparison (MAIC) was undertaken using an external CP arm.
METHODS: The InterAACT trial established CP as a standard of care therapy in advanced SCAC. An unanchored MAIC comparing the retifanlimab plus CP arm of POD1UM-303 (using individual patient data) with the CP arm of InterAACT (using published aggregate data) was considered feasible and appropriate. Baseline characteristics considered prognostic and/or treatment-effect modifiers (TEMs) were identified with clinical expert input. In the base case, POD1UM-303 patients were reweighted to match InterAACT on age, extent of disease, and number of metastatic sites. Scenario analyses explored alternative covariate sets. Weighted Kaplan-Meier estimates and Cox models were used to estimate OS.
RESULTS: The base case MAIC retained a high effective sample size for retifanlimab plus CP (144.8/154; 94%), indicating substantial population overlap. Before weighting, the OS hazard ratio (HR) for retifanlimab plus CP versus CP was 0.63 (95% confidence interval [CI]: 0.40, 0.99; p=0.04). After weighting, the HR was 0.58 (95% CI: 0.37, 0.90; p=0.01). Scenario analyses were consistent, with HRs of 0.58 (95% CI: 0.38, 0.90; p=0.01) using strong prognostic/TEM variables only and 0.48 (95% CI: 0.29, 0.80; p=0.004) using all available candidate variables.
CONCLUSIONS: The MAIC provided supportive indirect evidence of improved OS with retifanlimab plus CP versus CP, with results consistent across scenario analyses and with crossover-adjusted within-trial estimates.