Updated results from the HIMALAYA Phase III trial reveal that AstraZeneca's Imfinzi (durvalumab) combined with Imjudo (tremelimumab) provides a sustained and clinically meaningful overall survival (OS) benefit at five years for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were ineligible for localized treatment. The data, presented at the European Society for Medical Oncology (ESMO) Congress 2024, mark the longest survival follow-up ever reported for a Phase III immunotherapy trial in this setting.
Significant Survival Advantage
The exploratory analysis at five years showed that a single priming dose of Imjudo added to Imfinzi, known as the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab), reduced the risk of death by 24% compared to sorafenib (HR 0.76; 95% CI: 0.65-0.89). An estimated 19.6% of patients treated with the STRIDE regimen were alive at five years, versus 9.4% of those treated with sorafenib.
In a subgroup analysis of patients who achieved disease control (complete or partial response, or stable disease), 28.7% of those treated with the STRIDE regimen were alive at five years, compared to 12.7% of patients treated with sorafenib. Further analysis of depth of response (DpR) indicated that patients on the STRIDE regimen experienced deeper responses, leading to longer survival compared to sorafenib.
Expert Commentary
Lorenza Rimassa, MD, Associate Professor of Medical Oncology, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, and a lead investigator in the HIMALAYA trial, stated, "Treatment with durvalumab plus tremelimumab for patients with advanced liver cancer doubled the overall survival rate at five years, a significant survival advantage over sorafenib that has also become even more pronounced over time. These data reinforce the use of this novel dual immunotherapy regimen and are an important milestone for patients with this devastating disease."
HIMALAYA Trial Details
The HIMALAYA trial is a randomized, open-label, multi-center, global Phase III trial evaluating Imfinzi monotherapy and the STRIDE regimen versus sorafenib in 1,324 patients with unresectable, advanced HCC who had not received prior systemic therapy and were not eligible for locoregional therapy. The primary endpoint was OS for the combination versus sorafenib. Key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate, and progression-free survival (PFS) for both the combination and Imfinzi alone.
Safety Profile
The safety profile of the STRIDE regimen remained consistent with the known profiles of each medicine, with no new safety signals observed during the extended follow-up. Serious treatment-related adverse events (Grade 3 or 4, including death) occurred in 17.5% of patients treated with the STRIDE regimen versus 9.9% of patients treated with sorafenib. No new events were reported after the primary analysis for STRIDE.
Current Approvals and Future Directions
Imfinzi in combination with Imjudo is approved for the treatment of adults with advanced or unresectable HCC in the US, EU, Japan, and several other countries. Imfinzi monotherapy is also approved in Japan for this indication. These results underscore the potential of the STRIDE regimen as a first-line treatment option for patients with advanced HCC, offering a significant improvement in long-term survival.
