Updated results from the phase III HIMALAYA study demonstrate a significant improvement in long-term survival for patients with unresectable hepatocellular carcinoma (uHCC) treated with the STRIDE regimen, a combination of durvalumab and tremelimumab. The 5-year analysis, presented at the European Society for Medical Oncology (ESMO) Congress 2024, revealed a doubling of the survival rate compared to sorafenib, establishing a new benchmark in the treatment of this challenging cancer.
The HIMALAYA trial enrolled 1,171 patients who were randomized to receive either STRIDE (tremelimumab 300 mg plus durvalumab 1500 mg every 4 weeks), sorafenib (400 mg twice daily), or durvalumab monotherapy (1500 mg every 4 weeks). The latest analysis, with a median follow-up of approximately 63 months, showed a 5-year overall survival rate of 19.6% in the STRIDE arm compared to 9.4% in the sorafenib arm, representing a 24% reduction in the risk of death (HR=0.76).
Enhanced Survival with Disease Control
Notably, the survival benefit was even more pronounced in patients who achieved disease control. In this subgroup, the 5-year survival rate was 28.7% with STRIDE compared to 12.7% with sorafenib. This finding underscores the importance of tumor response in predicting long-term outcomes with immunotherapy.
According to Dr. Lorenza Rimassa, Associate Professor of Medical Oncology at Humanitas University, "These results set a new benchmark, with one in five patients alive with STRIDE at 5 years."
Depth of Response and Survival
Exploratory analysis of the depth of response (DpR) showed that patients treated with STRIDE experienced deeper tumor responses, which correlated with longer survival. For example, at 60 months, 72.7% of patients in the STRIDE arm had a DpR > 75% compared to 33.3% in the sorafenib arm.
Consistent Safety Profile
Importantly, the safety profile of the STRIDE regimen remained consistent with previous analyses. The rate of treatment-related serious adverse events did not increase with longer follow-up, indicating that the combination is generally well-tolerated.
Dr. Ghassan Abou-Alfa, a co-investigator in the HIMALAYA trial, commented on the safety profile, stating, "The safety profile doesn’t change at 5 years. It’s incredible that we are able to see people function with limited adverse events… Patients can keep going on with their lives, coming in for one injection once a month, and that’s it."
Implications for Clinical Practice
The 5-year data from the HIMALAYA study provide compelling evidence for the long-term efficacy and safety of the STRIDE regimen in unresectable hepatocellular carcinoma. The results suggest that STRIDE should be considered as a first-line treatment option for patients with this aggressive cancer. The study also highlights the potential for dual immune checkpoint inhibition to improve outcomes beyond conventional measures of response.
