A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

• Published in: The oncologist (Dayton, Ohio) Vol. 29; no. 3; pp. 270 - e413
• Main Authors: Yu, Shawn, Yu, Menggang, Keane, Barry, Mauro, David M, Helft, Paul R, Harris, William P, Sanoff, Hanna K, Johnson, Matthew S, O’Neil, Bert, McRee, Autumn Jackson, Somasundaram, Ashwin
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.03.2024
• Subjects: Blood clot; Cancer; Care and treatment; Clinical Trial Results; Combined modality therapy; Development and progression; Hepatoma; Immunotherapy; Liver; Liver cancer; Medical prognosis; Methods; Pilot projects; Prognosis; Radiotherapy; Rare earth metals; Thrombosis; Transplantation; United States; pembrolizumab; glass Y90 radioembolization; hepatocellular carcinoma; immunotherapy; TARE
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1093/oncolo/oyad331

Abstract Background Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564). Methods Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. Results Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6). Conclusion In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016). This pilot study explored whether using immunotherapy drugs in combination with locoregional therapies for patients with non-metastatic hepatocellular carcinoma is safe and beneficial, using pembrolizumab every 3 weeks starting 1 week before initial Y90 radioembolization.