Durvalumab Plus Tremelimumab Improves Survival in Unresectable HCC

The combination of a single priming dose of tremelimumab plus durvalumab demonstrated superior efficacy and a favorable benefit-risk profile compared with sorafenib in patients with unresectable hepatocellular carcinoma, according to an abstract presented at the recent American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

“A single priming dose of tremelimumab (anti-CTLA-4) added to durvalumab (anti-PD-L1) in the STRIDE (Single T Regular Interval Durvalumab) regimen … showed encouraging clinical activity and limited toxicity in a phase 2 unresectable hepatocellular carcinoma study (Study 22, NCT02519348), suggesting single exposure to tremelimumab is sufficient to improve upon durvalumab activity,” explained first author Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center & Weill Medical College at Cornell University, New York, New York, and coauthors in the abstract background.

The open-label, multicenter, phase 3 HIMALAYA trial evaluated the efficacy and safety of STRIDE, durvalumab, and sorafenib in 1171 patients with unresectable hepatocellular carcinoma and no prior systemic therapy. Among participants, 393 were randomized to STRIDE, 389 to durvalumab, and 389 to sorafenib.

STRIDE significantly improved overall survival compared with sorafenib, according to the abstract. Objective response rates were 20.1% for STRIDE, 17.0% for durvalumab, and 5.1% for sorafenib.

The study identified no new safety signals. Rates of Grade 3/4 treatment-related adverse events were 25.8% with STRIDE, 12.9% with durvalumab, and 36.9% with sorafenib. Rates of Grade 3/4 hepatic treatment-related adverse events were 5.9% with STRIDE, 5.2% with durvalumab, and 4.5% with sorafenib. Finally, rates of treatment-related adverse events leading to discontinuation were 8.2% with STRIDE, 4.1% with durvalumab, and 11.0% with sorafenib.

“STRIDE is a proposed, novel, first-line standard of care systemic therapy for unresectable hepatocellular carcinoma,” researchers advised.

—Jolynn Tumolo

Reference
Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. Abstract presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. September 30 – October 1, 2022. doi:10.1200/JCO.2022.40.4_suppl.379