Updated 5-year data from the phase 3 HIMALAYA study reveals that the combination of single tremelimumab (Imjudo) with durvalumab (Imfinzi), known as STRIDE, significantly improves overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC). The study, presented at the European Society for Medical Oncology Congress 2024, establishes new benchmarks in uHCC treatment, with approximately one in five patients alive at five years.
Sustained Survival Benefit with STRIDE
The HIMALAYA study compared STRIDE (n = 393) to sorafenib (n = 389) in patients with uHCC. The median OS was 16.43 months in the STRIDE arm compared to 13.77 months in the sorafenib arm, with a hazard ratio of 0.76 (95% CI, 2-sided P =.0008). At 5 years, the overall survival rate for STRIDE was 19.6% compared to 9.4% for sorafenib. The median follow-up duration was 62.49 months for STRIDE and 59.86 months for sorafenib.
Lorenza Rimassa, MD, associate professor of medical oncology at Humanitas University, highlighted the significance of these findings: "This 5-year updated analysis of the HIMALAYA study presents the longest follow-up to date in phase 3 studies for uHCC. STRIDE sustained an OS benefit vs sorafenib and demonstrated unprecedented long-term survival benefit at 5 years."
Impact of Disease Control and Tumor Response
Patients who experienced disease control with STRIDE showed enhanced OS rates, with 28.7% alive at 5 years compared to 12.7% in the sorafenib arm. Notably, 3.1% of patients in the STRIDE arm achieved complete response, while none did in the sorafenib arm. Partial responses were observed in 17.0% of STRIDE patients versus 5.1% of sorafenib patients. Deeper tumor responses, including over 50% shrinkage, were associated with longer overall survival in the STRIDE arm.
HIMALAYA Study Design
The HIMALAYA study enrolled patients with confirmed uHCC, a Child-Pugh score of A, and Barcelona Clinic Liver Cancer stage B or C. Patients had no prior systemic therapy for HCC, no main portal vein thrombosis, and an ECOG performance status of 0 or 1. A total of 1171 patients were randomly assigned to three arms: STRIDE (tremelimumab 300 mg plus durvalumab 1500 mg every 4 weeks), durvalumab monotherapy (1500 mg every 4 weeks), and sorafenib (400 mg twice daily).
The primary objective was to determine the superiority of OS with STRIDE versus sorafenib. Secondary objectives included assessing noninferiority of OS with durvalumab compared with sorafenib, 36-month OS rate, safety, and investigator-assessed progression-free survival.
Safety Profile
The updated analysis revealed no new serious treatment-related adverse events (TRAEs) compared to the primary analysis. At the 5-year data cut-off, 17.5% of patients in the STRIDE arm experienced serious TRAEs, consistent with previous reports. Similarly, the sorafenib arm showed comparable rates of serious TRAEs at both the 5-year and primary data cut-offs.
Clinical Implications
The HIMALAYA study's 5-year data underscores the potential of the STRIDE regimen to transform the treatment landscape for uHCC. The sustained survival benefit and manageable safety profile position STRIDE as a promising option for patients with this challenging disease. The findings also suggest that conventional response measures may not fully capture the benefits of STRIDE, warranting further investigation into more comprehensive assessment methods.
