HIMALAYA (durvalumab)
Trial question
Is durvalumab noninferior to sorafenib in patients with unresectable HCC?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
15.0% female
85.0% male
N = 778
778 patients (118 female, 660 male).
Inclusion criteria: patients with unresectable HCC and no previous systemic treatment.
Key exclusion criteria: hepatic encephalopathy within past 12 months; clinically meaningful ascites; main portal vein tumor thrombosis; active or prior documented gastrointestinal bleeding.
Interventions
N=389 durvalumab (at a dose of 1,500 mg every 4 weeks).
N=389 sorafenib (at a dose of 400 mg BID).
Primary outcome
Median overall survival
16.56 months
13.77 months
16.6 months
12.4 months
8.3 months
4.1 months
0.0 months
Durvalumab
Sorafenib
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in median overall survival (16.56 months vs. 13.77 months; HR 0.86, 95% CI 0.73 to 1.03).
Secondary outcomes
No significant difference in median progression-free survival (3.65 months vs. 4.07 months; HR 1.02, 95% CI 0.88 to 1.19).
Safety outcomes
No significant difference in adverse events and grade 3 or 4 adverse events.
Conclusion
In patients with unresectable HCC and no previous systemic treatment, durvalumab was noninferior to sorafenib with respect to median overall survival.
Reference
Ghassan K Abou-Alfa, George Lau, Masatoshi Kudo et al. Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070.
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