Richard S. Finn, MD, on HCC: Tislelizumab vs Sorafenib, and Their Impact on Quality of Life

The RATIONALE-301 Study was a global randomized open label study whose primary endpoint was presented at ESMO 2022, which looked at the PD-1 antibody, tislelizumab, versus sorafenib in an open-label study with the primary endpoint being overall survival in patients with advanced liver cancer. This study was powered for non-inferiority and met its primary endpoint of demonstrating non-inferiority to sorafenib with a hazard ratio of 0.85. The upper limit of the confidence interval did cross one, but it was lower than the non-inferiority threshold. So initially presented were other secondary endpoints, such as an improvement in objective response rate, as well as a very clean safety profile for tislelizumab. Here at ASCO 2023 GI, we presented patient-reported outcomes and quality of life readouts from the study. These are pivotally important in modern oncology studies, especially when powered for non-inferiority, and we demonstrated that this monoclonal PD-1 antibody, tislelizumab, improved several patient-reported outcomes using several well-validated screening tools. There was a very high compliance with completing these tools and really supports the overall data that single-agent PD-1 inhibition with tislelizumab can play a role in frontline liver cancer. Even though the study did not improve survival versus sorafenib, the fact that the drug improved response rates, had a clean safety profile and improves and maintains quality of life, as compared to sorafenib, which we've had for a long time, which did improve survival but also has significant side effects which can affect quality of life. The landscape for liver cancer has changed. PD-1 doublets are being used, atezo/bev. More recently, Durva/Treme was approved. We also have the TKIs, such as lenvatinib and sorafenib. But I think there's still probably a role for single-agent PD-1 inhibition for some patients, and especially now we have level one evidence that tislelizumab is active in the frontline and has a better quality of life profile, which is important for these patients who all have comorbidities, especially underlying liver disease, and it's not just improving their survival, but maintaining their quality of life that's important.