Real-world comparative outcomes of nivolumab + ipilimumab vs. atezolizumab + bevacizumab in advanced hepatocellular carcinoma: A TRINETX study

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. Atezolizumab plus Bevacizumab (ATZ+BEV) has transformed the treatment landscape for advanced HCC and is now a first-line option following the IMbrave150 trial. The Checkmate 040 randomized controlled trial has shown that Nivolumab plus Ipilimumab (NIVO+IPI) has improved long-term survival benefit. This study aims to compare outcomes of both treatment modalities for advanced HCC. Methods This is a retrospective cohort study utilizing the TriNetX database. Criteria included adult patients >18 years of age with Advanced HCC recently initiating (ATZ+BEV) or (NIVO+IPI). Outcomes are overall survival, the most recent AFP, AST, ALT, Bilirubin, INR, and Platelet count levels. Time to AFP to reach 0-40 ng/ml. Risk of developing hepatic encephalopathy or coma, hospitalization, and adverse events. Propensity score matching (PSM) was performed for demographics, lab results, MELD and ECOG scores, and confounding comorbidities. Results were expressed in the form of risk difference (RD) with 95% CI. Time to event endpoints using Kaplan-Meier curves and Cox proportional hazards models are reported as hazard ratios (HR) and log-rank P values. Results After matching, the cohort included 1979 patients in the (ATZ+BEV) group and 1973 patients in the (NIVO+IPI) group. (ATZ+BEV) showed significantly increased median survival 997 vs 504 days (HR 0.67, 95 % CI 0.61-0.74 log-rank p < 0.0001). However, mean AFP differed statistically (ATZ+BEV) 7,746 vs (NIVO+IPI) 17,495 p = 0.006. The time to normalization of AFP to below 40 was not significant (p = 0.196). (ATZ+BEV) Recipients experienced a high risk of inpatient visits (RD 2.08%, 95% CI -3.089, 7.257, P = 0.43). The risk of developing predefined adverse events was similar between regimens with nonsignificant RD. In conclusion, this real-world matched cohort (ATZ+BEV) conferred superior overall survival but was associated and greater healthcare utilization, while adverse event rates were comparable between treatments.