Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: A biomolecular exploratory, phase II trial

• Published in: European journal of cancer (1990) Vol. 174; pp. 68 - 77
• Main Authors: Lai, ZhiCheng, He, MinKe, Bu, XiaoYun, Xu, YuJie, Huang, YeXing, Wen, DongSheng, Li, QiJiong, Xu, Li, Zhang, YaoJun, Wei, Wei, Chen, MinShan, Kan, Anna, Shi, Ming
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2022; Elsevier Science Ltd
• Subjects: 5-Fluorouracil; Anticancer properties; Aspartate aminotransferase; Biomarkers; Chemotherapy; Hepatic arterial infusion chemotherapy; Hepatocellular carcinoma; High-risk advanced hepatocellular carcinoma; Hypertension; Lenvatinib; Liver; Liver cancer; Medical prognosis; Oxaliplatin; Patients; Predictive biomarkers; Risk; Thrombocytopenia; Toripalimab; BTC; High-risk advanced hepatocellular carcinoma; HAIC; Toripalimab; Hepatic arterial infusion chemotherapy; Predictive biomarkers; HCC; Lenvatinib; FOLFOX; CCL28; PD-1
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.07.005

The combination of lenvatinib, toripalimab and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) suggested encouraging antitumour activity in our retrospective study. We hereby prospectively establish the efficacy, safety and predictive biomarkers of the combination therapy as a first-line treatment in patients with high-risk advanced hepatocellular carcinoma (HCC). This phase II, single-centre, single-arm trial enrolled advanced HCC participants with high-risk. Of 51 screened participants, 36 received lenvatinib, toripalimab plus FOLFOX-HAIC. Participants received 21-day treatment cycles of lenvatinib, toripalimab, and FOLFOX-HAIC. The primary end-point was the progression-free survival (PFS) rate per RECIST at six months. Thirty-six participants (86.1% with high-risk features) were enrolled in our study. The primary end-point was met with a PFS rate of 80.6% (95% CI, 64.0%–91.8%) at six months. The median PFS was 10.4 months (95% CI, 5.8–15.0), and the median OS was not reached at the prespecified final analysis and was 17.9 months (95% CI, 14.5–21.3) after follow-up was extended. The ORR per RECIST was 63.9%, and per mRECIST was 66.7%. The median duration of response was 14.4 months (95% CI, 8.9–19.9). The most common adverse events were thrombocytopenia, elevated aspartate aminotransferase, and hypertension, and no treatment-related death was reported. Participants with low levels of both CCL28 and BTC had unsatisfactory prognosis. Lenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features. The levels of CCL28 and BTC might be the predictive biomarkers for the triple combination therapy. •High-risk advanced HCC is associated with poor outcomes of systemic therapy.•Combination FOLFOX-HAIC with lenvatinib and toripalimab was tolerable and effective.•CCL28 and BTC levels before therapy might be the predictive biomarkers of efficacy.