For a study, researchers sought to look into the possibility that the objective response (OR) functions as a stand-in endpoint and a separate OS predictor. Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to assess OS as a surrogate for OR in advanced HCC randomized clinical trials (RCT) reported between 2010 and 2020 modified RECIST (mRECIST). A meta-analysis combined RCTs that looked at the effect of OR on OS in a time-dependent multivariate analysis. They examined 34 trials with 14,056 patients that reported OS and OR by either RECIST (n=23), mRECIST (n=5), or both (n=6) out of 65 RCTs that were discovered in advanced HCC. When surrogacy was taken into consideration, the OR odds ratio and OS HR had a trial-level association with R=0.677 by mRECIST and R=0.532 by RECIST. Patients with OR by mRECIST had a pooled HR for OS of 0.44 (95% CI, 0.27-0.70; P<0.001) compared to nonresponders, according to a meta-analysis of 5 RCTs that evaluated factors influencing survival in multivariate analysis. OS was more affected by reactions to atezolizumab-bevacizumab than by reactions to tyrosine kinase inhibitors. Patients with advanced HCC can predict their OS accurately with OR-mRECIST. Surrogacy was not overused, although OR-mRECIST and OS had a stronger correlation than OR-RECIST. Although it can be used as an endpoint in phase II proof-of-concept studies, the evidence did not support using it as a primary endpoint in phase III trials examining systemic medicines.
