Llovet JM, et al. - In this investigation, researchers analyzed the reasons for positive or negative phase III trials in advanced hepatocellular carcinoma (HCC), a relevant cause of cancer-related mortality worldwide, and the strengths and limitations of clinical surrogate endpoints (progression-free survival [PFS], time to progression [TTP] and objective response rate [ORR]) to predict survival. A thorough analysis of 21 phase III trials published in advanced HCC showed a moderate association between PFS or TTP with overall survival (OS). In 3 out of 7 Phase III studies, however, significant differences in PFS were only followed by differences in survival. The magnitude of benefit for PFS in these later cases was HR 0.6, and this threshold is thus proposed as a potential surrogate endpoint of OS in advanced HCC. In contrast, despite being significant, PFS with an HR between 0.6-0.7 was not associated with better survival, and therefore these magnitudes are considered to be uncertain surrogates.