The clinical implications of trial endpoints in immunotherapy for hepatocellular carcinoma

Investigative work in the treatment of hepatocellular carcinoma is rapidly growing with the advent of immunotherapy. Nonetheless, trial endpoints and, more importantly, clinically meaningful endpoints need to be accurately chosen depending on the phase of trial and the patient population studied. We provide a scoping review focusing on trial endpoints on the use of immunotherapy in hepatocellular carcinoma.

We searched PubMed and Google Scholar for prospective phase II and III trials using immunotherapy, whether in the neoadjuvant, adjuvant, bridging, downstaging, or palliative settings, while discussing the clinical implications of trial endpoints.

The field of immune oncology is rapidly progressing and has become the standard of care in advanced hepatocellular carcinoma. However, the role of immunotherapy in the treatment of early and intermediate stage hepatocellular carcinoma is yet to be defined. Prospective trials for all stages of disease must strive for endpoints that are not only statistically significant but also clinically consequential. Whereas overall response rate may be a reasonable trial endpoint in phase II trials, phase III trials should rather aim for the improvement of overall survival or quality of life to have clinically meaningful impacts.