Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

Xiao-Dong Zhu; Cheng Huang; Ying-Hao Shen; Yuan Ji; Ning-Ling Ge; Xu-Dong Qu; Lingli Chen; Wen-Kai Shi; Mei-Ling Li; Jin-Jin Zhu; Chang-Jun Tan; Zhao-You Tang; Jian Zhou; Jia Fan; Hui-Chuan Sun

doi:10.1159/000514313

Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

Liver Cancer. 2021 Jul;10(4):320-329. doi: 10.1159/000514313. Epub 2021 Mar 30.

Authors

Xiao-Dong Zhu¹, Cheng Huang¹, Ying-Hao Shen¹, Yuan Ji², Ning-Ling Ge³, Xu-Dong Qu⁴, Lingli Chen², Wen-Kai Shi⁵, Mei-Ling Li¹, Jin-Jin Zhu¹, Chang-Jun Tan¹, Zhao-You Tang¹, Jian Zhou¹, Jia Fan¹, Hui-Chuan Sun¹

Affiliations

¹ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Hepatic Oncology, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported.

Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated.

Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4-8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8-15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence.

Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

Keywords: Anti-PD-1 antibody; Anti-angiogenic therapy; Conversion therapy; Hepatocellular carcinoma.