Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

SPS commentary:

A commentary discusses lessons from the CheckMate 459 study. First, only 56.3% of the screened patients were included, reflecting the large proportion of patients with hepatocellular carcinoma who are still excluded from clinical trials without receiving evidence-based treatment. Also of interest, and challenging the usual treatment discontinuation on tumour progression, 32%, of patients in the nivolumab group and 41% of patients in the sorafenib group continued on treatment beyond progression, which might have allowed a sustained benefit, as progression at radiology does not unequivocally reflect treatment failure. Furthermore, overall survival and objective response rate were also reported according to tumour PD-L1 expression (≥1% and <1%), which provide another informative lesson that could be key to understanding patient outcome: despite more progression and a higher objective response rate in the nivolumab group, both treatment groups had similar overall survival, which means that pattern of progression might also have a role in treatment outcome. Lastly, it notes the availability of several effective therapies for different treatment phases might suggest abandonment of overall survival as the unique robust primary endpoint. However, progression-free survival has not been validated as a surrogate for overall survival and development of novel endpoints that could replace it should be a priority.