Anti–PD-1 Antibody Combined with Drug-eluting Bead Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria

Abstract

Introduction: The aim of this study was to investigate the potential value of the combined drug-eluting bead (DEB)-TACE and anti–PD-1 antibody (Sintilimab) as preoperative treatment for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A/B HCC beyond the Milan Criteria. Methods: This is a prospective phase II pilot study involving patients with BCLC stage A/B HCC beyond the Milan criteria. DEB-TACE therapy was started together with the first dose of Sintilimab (200mg every three weeks). Repeated TACE was performed on demand. Safety and tumor response were routinely assessed, and further decisions were made in a multidisplinary manner. If necessary, surgical resection occurs within 8 weeks after the last DEB-TACE treatment. Results: Sixty-one patients—of whom 52.5% had BCLC stage B disease— underwent 144 cycles of therapy (DEB-TACE in combination with Sintilimab, 73 cycles; Sintilimab alone, 71 cycles). The median number of DEB-TACE sessions per patient was two (range, one to three cycles), and the median doses of Sintilimab was 400 mg. Commonly reported adverse events included alterations of liver function (90.2%), fatigue (52.4%), pain (49.2%), the majority of which were grades 1-2. Objective response was observed in 36/60 evaluable patients using mRECIST criteria. 51 patients proceeded with surgical resection as judged by a multidisplinary team, and 47.9% of patients experienced major pathologic response (MPR) by pathological examination. Conclusion: The combination of PD-1 checkpoint inhibition and DEB-TACE is safe and effective as preoperative treatment in patients with BCLC A/B HCC beyond the Milan Criteria.