Real-World STRIDE Validates Survival Benefit in Advanced HCC : JHEP Report | Mar 2026

Introduction

Durvalumab plus Tremelimumab (STRIDE regimen) has emerged as a first-line immunotherapy option for unresectable Hepatocellular Carcinoma following the pivotal HIMALAYA trial. However, real-world evidence regarding efficacy, safety and applicability in patients outside strict clinical trial eligibility criteria has remained limited.

Problem Statement

Patients encountered in routine hepatology and oncology practice frequently have impaired liver function, portal vein invasion, prior systemic therapy exposure or poor performance status, all of which were underrepresented in the HIMALAYA trial. Whether STRIDE maintains clinical effectiveness and tolerability in these higher-risk populations remains uncertain, particularly given the central impact of hepatic decompensation on survival outcomes in advanced HCC.

Summary

The international multicentre DT-real study evaluated real-world outcomes of durvalumab with or without tremelimumab in 233 patients with unresectable or advanced HCC treated across 35 centres. Approximately half of the cohort fulfilled key HIMALAYA eligibility criteria (HIMALAYA-IN), whereas the remaining patients (HIMALAYA-OUT) had more advanced liver dysfunction, poorer performance status, Vp4 portal invasion or prior systemic therapy exposure. Median overall survival in the entire cohort reached 20.4 months, confirming meaningful reproducibility of STRIDE efficacy outside clinical trials. Importantly, HIMALAYA-IN patients achieved a median survival of 23 months, substantially outperforming HIMALAYA-OUT patients, who demonstrated a median survival of 12.2 months. Disease control emerged as a major determinant of durable survival benefit, with long-term survival substantially improved among patients achieving complete response, partial response or stable disease. Macrovascular invasion and hepatic decompensation independently predicted mortality, reinforcing the dual prognostic importance of tumour burden and preservation of liver function during immunotherapy. Notably, hepatic decompensation occurred in approximately 10% of patients within one year, emphasizing that cirrhosis progression remains a critical competing risk even during effective oncologic therapy. The study also suggested that STRIDE may retain efficacy in selected patients with Vp4 portal invasion, potentially offering an important therapeutic alternative in patients unsuitable for anti-angiogenic combinations because of bleeding risk. Safety outcomes were acceptable and comparable to clinical trial experience, with grade 3–4 treatment-related adverse events occurring in 16% of patients. Skin toxicity and immune-mediated diarrhoea/colitis were the most frequent adverse events. Overall, this study validates the effectiveness of dual checkpoint inhibition in routine HCC practice while highlighting the importance of patient selection, liver function preservation and careful monitoring for hepatic decompensation during therapy.