Lenvatinib combined with PD1 in the treatment of advanced liver cancer

Lenvatinib plus anti-PD-1 antibody can be used as a conversion treatment for patients with unresectable intermediate-to-advanced hepatocellular carcinoma (HCC). More than 70% of patients with hepatocellular carcinoma are diagnosed at an advanced stage and lose the chance of radical surgery. Combination therapy with tyrosine kinase inhibitors (TKIs) lenvatinib and anti-programmed cell death protein-1 (PD-1) antibodies has achieved high tumor response rates in both first- and second-line treatment of advanced hepatocellular carcinoma.

In a single-arm phase II trial, patients received oral lenvatinib once daily and an intravenous anti-PD-1 drug every 3 weeks (one cycle) before the fourth cycle and then every two cycles to assess tumor response and resectability. The primary endpoint was investigator-assessed conversion success, and secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and 12-month recurrence-free survival (RFS), R0 resection rate, overall survival (OS), and safety as assessed by independent imaging review (IIR) according to modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors.

Results: Among the 56 patients included, 94.6% had large vessel invasion, and 28.6% had extrahepatic metastasis. The median follow-up time was 23.5 months. The primary endpoint showed a conversion success rate of 55.4%. ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. The median PFS was 8.9 months and the median OS was 23.9 months. Among 31 patients who were successfully transformed, 21 underwent surgery, with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Analysis of the tumor immune microenvironment of pretreatment samples showed a significant enrichment of CD8+ T cells in responders compared with non-responders. Therefore, lenvatinib plus anti PD-1 antibody as a conversion therapy for unresectable hepatocellular carcinoma has good efficacy and tolerable safety. Pre-existingCD8+ cells were identified as a promising biomarker of response to this regimen.

Lenvatinib The original drug has been launched in China and has entered the scope of Class B medical insurance. The price of 4mg*30 tablets per box may be more than 3,000 yuan. Lenvatiniboriginal drug currently marketed overseas, specificationsThe price of each box of 4mg*30 tablets may be more than 1,000 yuan (the price may fluctuate due to exchange rate effects). Lenvatinib generic drugs are also produced and marketed overseas. Their drug ingredients are basically the same as those of the original drugs sold domestically and abroad, but the price is cheaper. For example, the price of a box of 4mg*30 tablets produced by a Bangladesh pharmaceutical factory may be RMB 800 (the price may fluctuate due to exchange rates).