Safety and Efficacy of Immunotherapy in Clinical Trials

Three immunotherapy-based regimens have transformed first-line treatment for people with unresectable hepatocellular carcinoma (HCC): atezolizumab plus bevacizumab (IMbrave150), durvalumab plus tremelimumab (HIMALAYA), and nivolumab plus ipilimumab (CheckMate 9DW). These trials marked a significant advancement from the era when sorafenib offered only 2 to 3 months of survival benefit. The focus has appropriately shifted from surrogate end points to overall survival and, critically, to long-term survival outcomes that matter most to patients.

Yarchoan emphasizes that patients care less about incremental monthly improvements in median survival and more about their chances of reaching meaningful milestones—graduations, weddings, anniversaries. The immunotherapy trials now provide these data, with median overall survival reaching 19.2 months with atezolizumab-bevacizumab, 16.5 months with durvalumab-tremelimumab, and 23.7 months with nivolumab-ipilimumab. Long-term follow-up continues for HIMALAYA and CheckMate 9DW, though IMbrave150 did not collect extended survival data beyond the trial period.

Importantly, control arms in contemporary trials show improving outcomes—even sorafenib and lenvatinib achieved 19 to 20 months median survival in CheckMate 9DW—suggesting better overall patient management and effective subsequent therapies. This improvement across all treatment arms reflects the field’s growing expertise in managing this disease. While these regimens were not compared head-to-head, making direct comparisons difficult, all 3 demonstrate clear superiority over tyrosine kinase inhibitors in terms of survival, response rates, and the potential for durable complete responses that raise the possibility of cure for select patients.