Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of Hepatology, S0168827825002260. https://doi.org/10.1016/j.jhep.2025.03.033 Dr. Lorenza Rimassa et al.
Points
- The HIMALAYA study is the first phase III trial to report 5-year overall survival data for patients with unresectable hepatocellular carcinoma, setting a new clinical research milestone.
- After five years, the STRIDE immunotherapy regimen demonstrated a significant overall survival benefit, with 19.6% of patients still alive, compared to 9.4% of those treated with sorafenib.
- The treatment maintained a manageable safety profile over the long-term follow-up, with no new or late-onset serious adverse events reported for the STRIDE combination therapy.
- Improved survival was associated with any degree of tumor shrinkage, suggesting conventional response criteria may not fully capture the clinical benefits of the STRIDE immunotherapy regimen.
- This extended long-term survival with STRIDE occurred across all key patient subgroups, establishing a new benchmark with one in five patients alive at five years.
Summary
A new exploratory analysis of the phase III HIMALAYA trial reports 5-year overall survival (OS) outcomes for patients with unresectable hepatocellular carcinoma (uHCC). The study compared the STRIDE regimen (a single priming dose of tremelimumab plus durvalumab) against sorafenib monotherapy. With a median follow-up of 62.49 months for the STRIDE arm and 59.86 months for the sorafenib arm, the STRIDE regimen demonstrated a sustained and significant OS benefit, establishing it as the first phase III immunotherapy treatment to report 5-year survival data in this patient population.
The analysis confirmed a favorable hazard ratio (HR) for OS of 0.76 (95% CI 0.65-0.89) for STRIDE versus sorafenib. At 60 months, the OS rate was 19.6% for STRIDE compared to 9.4% for sorafenib. This benefit was more pronounced in patients who achieved disease control (OS rate: 28.7% vs. 12.7%) or experienced significant tumour shrinkage of over 25% (OS rate: 50.7% vs. 26.3%). Furthermore, there were more extended long-term survivors (≥48 months) in the STRIDE arm (21.1%) than in the sorafenib arm (11.6%), with no new late-onset treatment-related serious adverse events reported in the STRIDE arm.
These findings suggest that any degree of tumour shrinkage with STRIDE is associated with improved OS, indicating that conventional response metrics like RECIST v1.1 may not fully capture the regimen’s clinical benefit. However, patients with the most profound responses tend to derive the most significant long-term benefits. By demonstrating that one in five patients treated with STRIDE is alive at five years, the HIMALAYA study establishes a new survival benchmark in uHCC, providing crucial long-term efficacy and safety data to guide clinical decision-making.
Link to the article: https://www.journal-of-hepatology.eu/article/S0168-8278(25)00226-0/fulltext
References Rimassa, L., Chan, S. L., Sangro, B., Lau, G., Kudo, M., Reig, M., Breder, V., Ryu, M.-H., Ostapenko, Y., Sukeepaisarnjaroen, W., Varela, M., Tougeron, D., Crysler, O. V., Bouattour, M., Van Dao, T., Tam, V. C., Faccio, A., Furuse, J., Jeng, L.-B., … Abou-Alfa, G. K. (2025). Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. Journal of Hepatology, S0168827825002260. https://doi.org/10.1016/j.jhep.2025.03.033
