Reproducible safety and efficacy of durvalumab with or without tremelimumab for hepatocellular carcinoma in clinical practice: Results of the DT-real study.
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Celsa Ciro, Pressiani Tiziana, Nishida Naoshi, Chamseddine Shadi Mohamad, Arvind Ashwini, Li Michael, Fortuny Marta, Khaled Najib Ben, Iavarone Massimo, Toyoda Hidenori, Rapposelli Ilario Giovanni, Casadei-Gardini Andrea, Vivaldi Caterina, Ulahannan Susanna, Andanamala Haripriya, Scheiner Bernhard, Pinter Matthias, Orlandi Elena, Fulgenzi Claudia A M, Manfredi Giulia F, Lombardi Pasquale, D'Alessio Antonio, Stefanini Bernardo, Villani Rosanna, Ponziani Francesca Romana, Stella Leonardo, Carminati Ornella, Ricci Angela Dalia, Gonzalez Melina, Sparacino Alba, Di Maria Gabriele, Vaccaro Marco, Cabibbo Giuseppe, Cammà Calogero, Reig Maria, Kelley Robin K, Singal Amit G, Kaseb Ahmed O, Kudo Masatoshi, Rimassa Lorenza, Pinato David James
Аннотация
METHODS: From a database of 1,423 patients with advanced/unresectable HCC treated with immunotherapy across 35 centres, we analysed 233 patients receiving STRIDE or durvalumab monotherapy. Patients were categorized as HIMALAYA-IN or HIMALAYA-OUT based on key trial eligibility criteria (no prior systemic therapy, ECOG-PS 0-1, Child-Pugh class A, no Vp4 thrombosis). Baseline characteristics were assessed for overall survival (OS) and hepatic decompensation using a multivariable Cox model and competing-risk analysis, respectively. Objective response rates and treatment-related adverse events were recorded.
RESULTS: Of the 233 patients, 123 (53%) were HIMALAYA-IN and 110 (47%) were HIMALAYA-OUT. STRIDE was given in 95% of HIMALAYA-IN patients. After median follow-up of 6.0 months, median OS was 20.4 months (95% CI 11.7-NR) in the overall population. HIMALAYA-IN patients achieved significantly longer OS than HIMALAYA-OUT patients (23.0 vs. 12.2 months; hazard ratio 0.61; 95% CI 0.39-0.96; p = 0.03). Macrovascular invasion and hepatic decompensation were independent negative prognostic factors in the whole cohort. Hepatic decompensation occurred in 10.5% of patients within 12 months from treatment start. Objective response rate was 23.7% and 17.8% of HIMALAYA-IN and -OUT patients, respectively. Patients achieving disease control (whole cohort: 59.4%) demonstrated 24-month OS of 58.2% in HIMALAYA-IN and 44.8% in HIMALAYA-OUT groups. Grade 3-4 treatment-related adverse events occurred in 16.3% of patients.
CONCLUSIONS: STRIDE shows reproducible effectiveness and an acceptable safety profile in real-world practice. Achieving disease control and maintaining liver function emerged as key determinants of long-term survival benefit.
IMPACT AND IMPLICATIONS: The DT-real study validates the efficacy and safety of STRIDE (durvalumab plus tremelimumab) in routine clinical practice, with HIMALAYA trial-eligible patients achieving 23-month median survival, and showing a safety profile comparable to that observed in the pivotal trial. Nearly half of real-world patients received treatment despite not meeting original trial criteria, reflecting urgent clinical need in this population with limited therapeutic options. As for other immunotherapy-based combinations, hepatic decompensation is a critical determinant of survival. Patients achieving disease control demonstrated substantially improved 24-month overall survival rates compared to those with progressive disease, confirming the findings of the exploratory analyses of the HIMALAYA trial.