Estimating Long-Term Survival in the Face of Immature Data: A Case Study of Nivolumab in Second Line Renal Cell Carcinoma

OBJECTIVES: The clinical trial of nivolumab in second line renal cell carcinoma (CheckMate-025) was stopped early after meeting prespecified overall survival (OS) gains in an interim analysis. This study aims to illustrate the added benefit of long-term registry data in the selection of the survival extrapolation curves in a case with 14 months' minimum follow-up. METHODS: We compared different OS extrapolations on statistical fit criteria and alignment with RCC registry data. NICE (UK), NoMA (Norway), and TLV (Sweden) respectively selected the single generalized gamma (single-GG), independent gamma (indep-G), and single log-logistic (single-LL) curves based on the 14-months dataset We used a 26-months dataset of OS, unavailable at the time of the original extrapolation decisions, to assess the predictive value and stability of the extrapolations. RESULTS: All HTA agency extrapolations underestimated OS compared to the Norwegian and Swedish registry data, though the single-LL curve matched the registry data most closely. Predicted OS estimates based on the 14-months dataset, using single-GG, indep-G, and single-LL models, matched the observed survival recorded in the 26-months dataset. Refitting the curves to the 26-months data showed substantial differences in mean OS estimates compared to the 14-month data for the indep-G curve (A=7.7%).The other two curves provided similar OS estimates, irrespective of the dataset used (A