Effectiveness and Safety of the PD-1 Inhibitor Lenvatinib Plus Radiotherapy in Patients with HCC with Main PVTT: Real-World Data from a Tertiary Centre

Abstract

Guangxin Li,1,* Ying Zhao,1,* Keren Li,2,* Shizhong Yang,2 Canhong Xiang,2 Jiyong Song,3 Yanmei Yang,1 Gong Li,1 Jiahong Dong2,4 1Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 3Department of Liver Transplantation, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 4Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong Li; Jiahong Dong, Email [email protected]; [email protected]: Patients with hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT), especially type Vp-4, usually have a poor prognosis. However, the vast majority of Phase III clinical trials exclude this population based on the inclusion criteria. Lenvatinib plus a PD-1 inhibitor has shown promising antitumour activity and tolerable safety in patients with unresectable HCC in Asian populations. Radiotherapy has also demonstrated high response rates and favourable survival for HCC patients with PVTT. This study aimed to explore the preliminary clinical efficacy and safety of lenvatinib plus the PD-1 inhibitor combined with radiotherapy for HCC patients with main portal vein tumour thrombus.Methods: Between 1 March 2018 and 31 October 2020, HCC patients with main PVTT who received lenvatinib plus a PD-1 inhibitor (pembrolizumab, nivolumab or sintilimab) combined with radiotherapy from Beijing Tsinghua Changgung Hospital in China were reviewed for eligibility. The efficacy was evaluated by the survival and PVTT response rate, and the safety was evaluated by the frequency of key adverse events (AEs).Results: In total, 39 eligible HCC patients with type Vp-4 PVTT who received triple therapy were included in this study. The 2-year OS rate was 15.4%, which was the primary end-point of our study. The median overall survival (OS) and progression-free survival (PFS) were 9.4 months (range 2.3 to 57.1) and 4.9 months (range 1.4 to 36.1), respectively. The objective response rate (ORR) of PVTT based on mRECIST was 61.5%. AFP dropped to normal 3 months after radiotherapy and was an independent risk factor associated with OS. All AEs were controlled, and no treatment-related deaths occurred.Conclusion: Lenvatinib plus PD-1 inhibitor combined with radiotherapy had a significant therapeutic effect and manageable AEs in HCC patients with type Vp-4 PVTT and may be a potential treatment option for advanced HCC.Keywords: hepatocellular carcinoma, portal vein tumour thrombus, lenvatinib, PD-1 inhibitor, radiotherapy

Keywords

• hepatocellular carcinoma
• portal vein tumour thrombus
• lenvatinib
• pd-1 inhibitor
• radiotherapy