Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC.
Objective: In the phase III HIMALAYA study (NCT03298451), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib in unresectable HCC (uHCC) and demonstrated long-term survival benefits. We report an updated exploratory analysis of OS with 5 years of follow-up, including survival by multiple tumour response measures.
Methods: Participants were randomised to STRIDE (tremelimumab plus durvalumab), durvalumab or sorafenib. OS, depth of response and serious adverse events (AEs) were assessed. Extended long-term survivors (eLTS; ≥48 months beyond randomisation) were described. Updated data cut-off: 01 March 2024.
Results: Median (95% CI) follow-up durations were 62.49 (59.47-64.79) months (STRIDE) and 59.86 (58.32-61.54) months (sorafenib). The OS HR (95% CI) for STRIDE versus sorafenib was 0.76 (0.65-0.89). OS rates at 60 months for STRIDE versus sorafenib were 19.6% versus 9.4% overall, 28.7% versus 12.7% in participants achieving disease control per RECIST v1.1 and 50.7% versus 26.3% in participants achieving >25% tumour shrinkage. No late-onset treatment-related serious AEs were reported for STRIDE. There were more eLTS with STRIDE (83/393, 21.1%) than sorafenib (45/389, 11.6%), and extended long-term survival occurred across all clinically relevant subgroups.
Conclusions: At 5 years, STRIDE sustained an OS benefit versus sorafenib and maintained a manageable safety profile. OS benefit with STRIDE was improved in participants with disease control. Data suggest that any degree of tumour shrinkage with STRIDE can be associated with improved OS, indicating that conventional response measures may not fully capture STRIDE benefits. Nevertheless, participants experiencing deep responses appear to have the greatest benefit. STRIDE continues to set new benchmarks in uHCC with 1 in 5 patients alive at 5 years. The phase III HIMALAYA study showed that STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) versus sorafenib in participants with unresectable HCC (uHCC), including after 4 years of follow-up. Understanding the efficacy and safety of STRIDE over the longer term is important for healthcare providers; here, we demonstrate that STRIDE sustained an OS benefit versus sorafenib and maintained a manageable safety profile after 5 years of follow-up. OS benefit with STRIDE was improved in participants with disease control and any degree of tumour shrinkage, indicating that conventional response measures may not fully capture the benefits of STRIDE. These findings are important as they set new benchmarks in uHCC and may help guide clinical decisions in the future.