A Retrospective Analysis of Conversion Therapy with Lenvatinib, Sintilimab, and Arterially-Directed Therapy in Patients with Initially Unresectable Hepatocellular Carcinoma

Leijuan Gan,1– 3,* Mengran Lang,1– 4,* Xindi Tian,1– 3 Shaohua Ren,1– 3 Guangtao Li,1– 3 Yayue Liu,1– 3 Ruyu Han,1– 3 Kangwei Zhu,1– 3 Huikai Li,1– 3 Qiang Wu,1– 3 Yunlong Cui,1– 3 Wei Zhang,1– 3 Feng Fang,1– 3 Qiang Li,1– 3 Tianqiang Song1– 3 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 4Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang, Hebei, 065001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianqiang Song, Tel +86-022-23340123, Fax +86 022-23537796, Email songtianqiangtj@163.comPurpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC).Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2– 47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥ 3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments.Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.Keywords: lenvatinib, sintilimab, conversion therapy, unresectable hepatocellular carcinoma, TACE, HAIC