Selective internal radiation therapy with yttrium-90 resin microspheres followed by lenvatinib plus PD-1 inhibitor for large or huge advanced-stage hepatocellular carcinoma: A retrospective cohort study from China.

581 Background: Yttrium-90 resin microspheres have been introduced into China in recent years, but the efficacy or safety on Chinese patients are rarely reported. This study aimed to evaluate the efficacy and safety of selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres followed by lenvatinib and PD-1 inhibitor in Chinese patients with large (5.1–10.0 cm in diameter) or huge (>10.0 cm) advanced-stage hepatocellular carcinoma (HCC). Methods: Data of large or huge Barcelona Clinic Liver Cancer stage C HCC patients treated with SIRT followed by lenvatinib plus PD-1 inhibitor from November 2022 to October 2023 were prospectively collected and retrospectively analyzed. Key endpoints included overall survival (OS), progression-free survival (PFS), complete response rate (CRR), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and adverse events (AEs) graded based on Common Terminology Criteria for Adverse Events v5.0. Risk factors affecting PFS were analyzed using univariate and multivariate Cox regression models. Results: A total of 30 patients (27 males, 3 females; mean age 54 ± 11 years) were included. The mean longest diameter of the tumor was 9.6 ± 4.2 cm (range: 5.2–17.6 cm). Nineteen (63.3%) patients had more than three intrahepatic lesions, 15 (50.0%) had vascular invasion, and 13 (43.3%) had extrahepatic metastasis. Sixteen (53.3%) patients had undergone prior anticancer therapies. Two patients received two SIRT procedures, and the rest had one. Lenvatinib and PD-1 inhibitor treatment was initiated 3–7 days after the initial SIRT procedure. CRR was 20.0%, ORR was 73.3%, and DCR was 90.0%. Median PFS was 8.0 months (95% CI, 5.6–10.4), and median OS was not reached. OS rates at 6, 12, and 18 months were 93%, 74%, and 74%, respectively. Univariate and multivariate analysis indicated that baseline alpha-fetoprotein levels, baseline eosinophil count, and neutrophil-to-lymphocyte ratio at 1 month after SIRT were independent risk factors for PFS. AEs of any grade occurred in 86.7% of patients, with grade 3 AEs in 23.3%, and no grade 4/5 AEs were recorded. Conclusions: SIRT followed by lenvatinib and PD-1 inhibitor demonstrates promising efficacy and a favorable safety profile in Chinese patients with large or huge advanced-stage HCC.