|The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2022. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
A single priming dose of tremelimumab added to durvalumab (STRIDE regimen) significantly improved overall survival (OS), compared with sorafenib monotherapy, as first-line treatment for patients with unresectable hepatocellular carcinoma (HCC), according to results of the phase 3 HIMALAYA study.
The results were presented at the ASCO Gastrointestinal Cancers Symposium 2022 by Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
The HIMALAYA trial (ClinicalTrials.gov Identifier: NCT03298451) enrolled patients with unresectable HCC who had not received prior systemic therapy. Dr Abou-Alfa noted that the trial population was heterogeneous and representative of patients with unresectable HCC worldwide.
The patients were randomly assigned to 1of 3 treatment regimens: STRIDE (393 patients), durvalumab monotherapy (389 patients), and sorafenib monotherapy (389 patients). Baseline characteristics were well balanced across the arms.
The study’s primary endpoint was met, as OS was significantly longer with the STRIDE regimen than with sorafenib. The median OS was 16.4 months and 13.8 months, respectively (hazard ratio [HR], 0.78; 96% CI, 0.65-0.92; P =.0035).
In addition, the OS with durvalumab monotherapy was noninferior to the OS with sorafenib. The median OS was 16.6 months in the durvalumab arm and 13.8 months in the sorafenib arm (HR, 0.86; 96% CI, 0.73-1.03).
The 2-year OS rate was 40.5% in the STRIDE arm, 39.6% in the durvalumab arm, and 32.6% in the sorafenib arm. The 3-year OS rates were 30.7%, 24.7%, and 20.2% respectively.
The median progression-free survival was 4.1 months in the sorafenib arm, 3.8 months in the STRIDE arm (HR, 0.90; 95% CI, 0.77-1.05), and 3.7 months in the durvalumab arm (HR, 1.02; 95% CI, 0.88-1.99).
The objective response rate was 20.1% in the STRIDE arm, 17.0% in the durvalumab arm, and 5.1% in the sorafenib arm. The median duration of response was 22.3 months, 16.8 months, and 18.4 months, respectively.
Grade 3/4 treatment-related adverse events (TRAEs) were observed in 25.8% of patients in the STRIDE arm, 12.9% in the durvalumab arm, and 36.9% in the sorafenib arm. The rate of grade 3/4 hepatic TRAEs was low across the arms — 7.0%, 5.2%, and 4.8%, respectively.
Serious TRAEs occurred in 17.5% of patients in the STRIDE arm, 8.2% in the durvalumab arm, and 9.4% in the sorafenib arm. Treatment-related deaths occurred in 2.3%, 0%, and 0.8%, respectively.
The 9 treatment-related deaths in the STRIDE arm were due to immune-mediate hepatitis (n=2), nervous system disorder (n=1), acute respiratory distress syndrome (n=1), hepatitis (n=1), myocarditis (n=1), pneumonitis (n=1), hepatic failure (n=1), and myasthenia gravis (n=1). The 3 treatment-related deaths in the sorafenib arm were due to hematuria, cerebral hematoma, and hepatic failure.
Based on these results, Dr Abou-Alfa concluded that the STRIDE regimen and durvalumab monotherapy “may represent new treatment options for patients with unresectable HCC.”
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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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. Presented at ASCO GI 2022; January 20-22, 2022. Abstract 379.