Overall survival (OS) validated surrogate endpoints are crucial for accelerating the clinical trial and medication development processes. For a study, researchers sought to confirm objective response in patients with unresectable hepatocellular carcinoma (HCC) undergoing systemic anti-angiogenic treatment as an independent predictor of OS.

In REFLECT, a phase III research comparing lenvatinib with sorafenib, they looked at the relationship between objective response (investigator-assessed mRECIST, independent radiologic review [IRR] mRECIST, and RECIST v1.1) and OS. At 2, 4, and 6 months following randomization, they conducted landmark analyses (Simon-Makuch) of OS by the objective response.

According to investigator-assessed mRECIST, the median OS for responders was 21.6 months (95% CI 18.6-24.5), compared to 11.9 months (95% CI 10.7-12.8) for non-responders (hazard ratio [HR] 0.61; 95% CI 0.49-0.76; P< 0.001). The connection between RECIST v1.1 and mRECIST was objectively supported (HR 0.61; 95% CI 0.51-0.72; P< 0.001 and HR 0.50; 95% CI 0.39-0.65; P< 0.001, respectively). OS was considerably longer for responders compared to non-responders (investigator-assessed mRECIST) at the 2-month (HR 0.61; 95% CI 0.49-0.76; P< 0.001), 4-month (HR 0.63; 95% CI 0.51-0.80; P< 0.001), and 6-month (HR 0.68; 95% CI 0.54-0.86; P< 0.001) milestones. Both mRECIST and RECIST v1.1 produced results that were comparable when evaluated by IRR. In a multivariate exploratory Cox regression analysis, the objective response by investigator-assessed mRECIST (HR 0.55; 95% CI 0.44-0.68; P< 0.0001) and IRR-assessed RECIST v1.1 (HR 0.49; 95% CI, 0.38-0.64; P< 0.0001) were found to be independent predictors of OS in people with unresectable HCC.

In REFLECT; the objective response was an independent predictor of OS in patients with unresectable HCC; more research was required to establish surrogacy formally. Compared to those with stable/progressive/non-evaluable illness, those who achieved a full or partial response by mRECIST or RECIST v1.1 had considerably longer lives.

Reference: journal-of-hepatology.eu/article/S0168-8278(22)03111-7/fulltext