Lovastinib for the treatment of first-line hepatocellular carcinoma

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Based on data from the REFLECT phase III trial, the US Food and Drug Administration (FDA) approved Lenvima as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). The test was published in The Lancet in February 2018. The test results showed that the multi-kinase inhibitor levatinib is superior to standard first-line therapy of sorafenib (Nexavar). The median overall survival (OS) of lovastinib was 13.6 months, while sorafenib was 12.3 months. Moreover, lovastinib is superior to sorafenib in both progression-free survival (PFS) and time to progression (TTP). Levatinib and sorafenib had median PFS of 7.4 and 3.7 months, and TTP of 8.9 and 3.7 months, respectively.

The REFLECT study randomly assigned 954 patients with unresectable HCC to the lovastinib group (n = 478) or the sorafenib group (n = 476). For patients with a weight of <60 kg, take levastinib 8 mg per day, and for patients with a weight of ≥60 kg, take levastinib 12 mg per day. The patients in the sorafenib treatment group took 400 mg twice daily.

The objective response rate (ORR) of lovastinib was 24.1%, while sorafenib was 9.2%. The complete remission rate (CR) of the lovastinib group was 1.3%, and sorafenib was 0.4%. The median duration of lovastinib response was 5.7 months, and sorafenib was 3.7 months. The median PFS of lovastinib and sorafenib were 7.3 and 3.6 months, respectively. The median TTP for this review was levatinib at 7.4 months and sorafenib at 3.7 months. Independent evaluation by the optimized RECIST standard showed that the improvement in ORR was more significant, with 40.6% in the lovastinib group and 12.4% in the sorafenib group. The CR of the lovastinib group was 2.1%, while the CR of the sorafenib group was 0.8%. For treatment-induced adverse events (TEAE), the lovastinib group accounted for 37%, while the sorafenib group accounted for 38%. The drug interruption caused by TRAE, the levatinib and sorafenib group accounted for 9% And 7%.

The most common TEAEs between levatinib and sorafenib are palm-plantar erythema paresthesia (27% and 52%, respectively), diarrhea (39% and 46%), and hypertension (42% and 30%) ). Compared with sorafenib, levastinib is more common in TEAEs of grade 3 or higher (57% and 49%, respectively). Compared with sorafenib, the levatinib group had more severe treatment-related TEAEs.

The most common grade 3 and grade 4 TRAEs, lovastinib and sorafenib were hypertension (23% and 14%), weight loss (8% and 3%), and increased blood bilirubin ( 7% and 5%), proteinuria (6% and 2%), thrombocytopenia (5% and 3%), aspartate aminotransferase increased (5% and 8%), decreased appetite (5% and 1%), diarrhea (4% and 4%) and palm-plantar erythema paresthesia (3% and 11%).

Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.

Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.

Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.

Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.

These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.

Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.

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