Comparative restricted mean survival time (RMST) analysis of survival in advanced hepatocellular carcinoma (aHCC) from pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW.

Abstract

597 Background: In advanced hepatocellular carcinoma (aHCC), the evaluation of overall survival (OS) and progression-free survival (PFS) through restricted mean survival time (RMST) provides a nuanced understanding of treatment efficacy. The RMST analysis serves as a valuable complement to the hazard ratio (HR) analysis, offering insights into the average survival time over a specified period. This study compares RMST analyses of OS at 24 and 36 months, and PFS at 12 and 18 months, across five pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW. Methods: Data from the experimental arms of the five phase III trials were analyzed. The RMST was calculated using the area under the Kaplan-Meier survival curves up to the specified time points. Specifically, OS was evaluated at 24 and 36 months, and PFS at 12 and 18 months. The RMST provides an estimate of the average time that patients survive (for OS) or remain progression-free (for PFS) within a specific timeframe. Kaplan-Meier survival curves were digitized if not available in raw form, and the area under the curve (AUC) was computed using numerical integration methods. RMST values were extracted from the AUC for the specified periods. This approach accounts for censored data and provides a robust comparison of survival times across different treatment groups. Results: The results for OS RMST at 24 and 36 months and PFS RMST at 12 and 18 months are summarized in the table. Conclusions: Angiogenesis inhibitor + immune checkpoint inhibitor combinations (Atezolizumab + Bevacizumab; Sintilimab + IBI305) provide the most favorable RMST outcomes in terms of OS and PFS. Restricted mean survival time (RMST) comparison of OS and PFS (months). aHCC 1L Phase III Trials Treatment Arm OS 24m OS 36m PFS 12m PFS 18m IMbrave-150 1, 2 Atezolizumab + Bevacizumab 17.50 22.79 9.69 13.29 ORIENT-32 3 Sinitilimab + IBI305 17.01 21.09 9.18 12.54 CARES-310 4 Camrelizumab + Rivoracenib 16.34 19.75 9.29 12.14 HIMALAYA 5, 6 Tremelimumab + Durvalumab 15.36 18.76 8.95 12.02 CM-9DW 7, 8 Nivolumab + Ipilimumab 15.87 20.08 8.74 11.78 1 Finn et al. N Engl J Med 2020;382:1894-905; 2 Cheng et al. J Hepatol 2022;76:862-873; 3 Ren et al. Lancet Oncol 2021;22:977–90; 4 Qin et al. Lancet 2023;402:1133–46; 5 Abou-Alfa et al. NEJM Evid 2022;1(8):EVIDoa2100070; 6 Sangro et al. Ann Oncol 2024;35:448-457; 7 Galle et al. J Clin Oncol 2024;42(suppl 17):abstr LBA4008; 8 Decaens et al. Ann Oncol 2024;35:S657.