A phase II trial of lenvatinib plus toripalimab and hepatic arterial infusion chemotherapy as a first-line treatment for advanced hepatocellular carcinoma (LTHAIC study).

Abstract

4083 Background: Combining systemic and locoregional therapies represents a promising treatment strategy for patients with advanced hepatocellular carcinoma (HCC). We investigated the efficacy and safety of combined lenvatinib and toripalimab (recombinant, humanized programmed cell death receptor-1 monoclonal antibody) plus hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment in this patient population. Methods: This single-arm, phase II study included treatment-naive adult (≥18 years) patients with advanced HCC, Eastern Cooperative Oncology Group performance status 0–2, and Child-Pugh Class A liver function (NCT04044313). Patients initiated lenvatinib (8 mg for bodyweight < 60 kg or 12 mg for bodyweight ≥60 kg, orally once daily) 3-7 days prior to initial HAIC to confirm tolerability, and then received 21-day treatment cycles of lenvatinib (day 1 to day 21), toripalimab (240 mg by IV infusion, on day 1), and HAIC (day 1 to day 2) with the FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 24 hours) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at six months, evaluated using RECIST 1.1. Secondary endpoints were median PFS and overall survival (OS), objective response rate (ORR) per RECIST 1.1 and mRECIST, and safety. Results: Between August 2019 and May 2020, 36 patients (33 men and 3 women; median age, 49 years) were enrolled. The median tumor size was 11.2 cm, 86.1% of patients had portal vein invasion, and 27.8% had extrahepatic metastasis. The primary endpoint showed a 6-month PFS rate of 80.6%. After a median follow up of 11.2 months, the median PFS was 10.5 months (95% CI, 6.21−14.79), and the median OS was not reached. The ORR per RECIST was 63.9% (95% CI, 40.9−73.0), and per mRECIST was 66.7% (95% CI, 43.3−75.1) including five (13.9%) patients who achieved a complete radiological response. The median duration of response was 12.1 months (95% CI, 4.52−19.69). Furthermore, eight patients achieved sufficient downstaging to be converted to resectable disease. Among them, one patient received liver transplantation, and four received curative surgical resection. One of them achieved pathological complete response. Grade 3-4 treatment-related adverse events (AEs) occurred in 72.2% of patients, and the most common were thrombocytopenia (13.9%), elevated aspartate aminotransferase (13.9%), and hypertension (11.1%). All AEs were expected and manageable, and no treatment-related deaths were reported. Conclusions: Combination treatment with lenvatinib and toripalimab plus HAIC showed promising antitumor activity and manageable toxicity in patients with advanced HCC. Further randomized, controlled trials are warranted to validate our findings. Clinical trial information: NCT04044313.

Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

“…In a retrospective analysis, the addition of toripalimab plus HAIF prolonged PFS and OS and increased ORR in HCC patients receiving lenvatinib ( 86 ). The effect of the combination regime was also explored in a prospective phase II trial, showing an ORR of 63.9% and median PFS of 10.5 months among 36 treatment-naive advanced HCC patients ( 87 ). Anlotinib, a novel multi-targeting tyrosine kinase inhibitor, has shown promising efficacy and safety as a first- or second-line treatment strategy in advanced HCC ( 88 ).…”

Efficacy and safety of monotherapy and combination therapy of immune checkpoint inhibitors as first-line treatment for unresectable hepatocellular carcinoma: a systematic review, meta-analysis and network meta-analysis

“…Eleven eligible studies were about combination therapy of ICIs and TKIs [41][42][43][44][45][46][47][48][49][50][51] involving 9 kinds of ICIs. The remaining three studies chose ICIs with ICIs, chemotherapy, and TKIs plus hepatic arterial infusion chemotherapy (HAIC) as first-line regimens, respectively [52][53][54].…”

Application of systemic treatment in conversion therapy options for liver cancer

“…Triple therapy (26)(27)(28)(29) Triple therapy shows promising antitumor activity and contributes to a higher conversion rate than Bigeminy therapy for patients in advanced HCC and PVTT.…”