A recent exploratory analysis of the phase III HIMALAYA trial involving patients with unresectable hepatocellular carcinoma (HCC) has shown that 1 in 5 participants (19.6%) treated with the STRIDE regimen (single tremelimumab regular interval durvalumab) remained alive after 5 years of follow-up vs 1 in 10 participants (9.4%) treated with sorafenib. These findings, published by Rimassa et al in the Journal of Hepatology, establish a new survival benchmark for people living with unresectable HCC.
Advanced HCC has historically carried a poor prognosis, with limited long-term survival largely due to late diagnosis and underlying advanced chronic liver disease. Previously reported results from the HIMALAYA study showed that participants treated with STRIDE, a combination regimen of the CTLA-4 inhibitor tremelimumab and the PD-L1 inhibitor durvalumab, lived longer than participants who received the multikinase inhibitor sorafenib (the standard of care at the time of the study’s design). Now, findings from this exploratory analysis determined how long participants lived after 5 years of follow-up and whether how long they lived was linked to changes in the size of their tumors after receiving treatment.
Lead investigator of the 5-year analysis, Lorenza Rimassa, MD, of Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, noted: “Our finding that one in five participants treated with STRIDE is alive after 5 years represents a key clinical breakthrough in the advancement of treatment for unresectable HCC. This remarkable 5-year survival in a phase III trial was unimaginable only a few years ago and sets an unprecedented milestone that will inform clinical practice for years to come.”
Key Findings
HIMALAYA is the first phase III study to report 5-year overall survival in unresectable HCC. At 5 years, STRIDE sustained an overall survival benefit vs sorafenib and manageable safety—there were no new, late-onset serious side effects reported related to STRIDE.
The overall survival rate at 5 years was 19.6% with STRIDE vs 9.4% with sorafenib, and participants who received durvalumab alone continued to live at least as long as those who received sorafenib. Overall survival with STRIDE was improved with disease control and any degree of tumor shrinkage, regardless of Response Evaluation Criteria in Solid Tumors version 1.1 response. Extended long-term overall survival with STRIDE occurred across all clinically relevant subgroups.
In an accompanying editorial, Pierre Nahon, MD, PhD, AP-HP, of Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; France, commented: “The most striking result of this analysis is that one in five patients treated with STRIDE remained alive after 5 years, a milestone that underscores the long-term potential of dual immunotherapy in unresectable HCC. The findings of this study offer a new horizon of hope for patients and health-care providers alike, reshaping clinical expectations and treatment goals in liver oncology.”
International coordinating investigator of the HIMALAYA trial, Ghassan K. Abou-Alfa, MD, JD, MBA, PhD, of the Department of Medicine, Memorial Sloan Kettering Cancer Center; Weill Medical College, Cornell University; and Trinity College, Dublin, Ireland, concluded: “Overall survival is often discussed as a statistical endpoint in clinical trials, but for patients, it carries more personal meaning. Patients are often most concerned with their individual likelihood of living for a certain number of years, surviving to attend key milestones—like a child’s graduation or traveling to see the world—while preserving their quality of life to enjoy time with loved ones. The findings we report in this long-term follow-up of the HIMALAYA study are worth celebrating and may help patients understand what these outcomes mean for them personally in terms of real time that may be gained.”
Disclosure: For full disclosures of the study authors, visit journal-of-hepatology.eu.
