Y90-radioembolization followed by nivolumab was safe and associated with an objective response rate of 30.6% in patients with advanced hepatocellular carcinoma, although the study did not meet its primary endpoint, investigators reported in Lancet Gastroenterology and Hepatology.
The single-arm, 2-stage, phase 2 CA 209-678 trial assessed the activity and safety of Y90-radioembolization followed by nivolumab in patients with advanced hepatocellular carcinoma at a cancer center in Singapore from January 18, 2017, to June 6, 2019.
Participants received intravenous nivolumab 240 mg at 21 days (±3 days) post-Y90-radioembolization, and again every 2 weeks until severe toxicities, progression, death, physician discretion, or withdrawal of consent occurred.
Objective response rate was the primary endpoint and was defined as the proportion of patients with a confirmed complete or partial response for lesions within and outside the Y90-radioembolization field according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
A total of 36 patients who received Y90-radioembolization and at least 1 full dose of nivolumab were included in the safety and efficacy endpoint analyses. The participants had a median age of 64 years, 78% were men, and 69% were Chinese.
Of the cohort, 1 patient had a complete response (2.8%; 95% CI, 0.07-14.5), 10 had a partial response (27.8%; 95% CI, 14.2-45.2), 11 had stable disease (30.6%; 95% CI, 16.4-48.1), and 11 had progressive disease (30.6%; 95% CI, 16.4-48.1).
After 3 patients were deemed nonevaluable, the objective response rate was 30.6% (95% CI, 16.4-48.1), and the study did not meet its primary endpoint.
For the 13 patients with extrahepatic spread, the objective response rate was 7.7% (95% CI, 0.2-36•0), 7.7% (95% CI, 0.2-36.0), and 23.1% (95% CI, 5.0-53.8) according to RECIST version 1.1, modified RECIST, and immune RECIST, respectively. In the 23 patients without extrahepatic spread, the objective response rate was 43.5% (95% CI, 23.2-65.5), 60.9% (95% CI, 38.5-80.3), and 43.5% (95% CI, 23.2-65.5), respectively.
A total of 29 (81%) patients had a treatment-related adverse event, with pruritus (18 patients [50%]) and maculopapular rash (13 patients [36%]) being the most common. Additionally, 5 (14%) patients had grades 3 to 4 treatment-related adverse events or serious adverse events.
Study limitations included patient and treatment heterogeneity and the single-arm and single-center design. Additionally, 10 patients did not have personalized dosimetry.
“This strategy should be further evaluated in patients with [Barcelona Clinic Liver Clinic B] disease that is refractory to or ineligible for transarterial chemoembolisation and patients with [Barcelona Clinic Liver Clinic B] disease without extrahepatic spread, and compared with systemic therapy alone in a randomised study,” researchers concluded.
Disclosure: This study was funded in part by Bristol-Myers Squibb and Sirtex. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Tai D, Loke K, Gogna A, et al. Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(12):1025-1035. doi: 10.1016/S2468-1253(21)00305-8