Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings.

Sasaki Sasaki,Fukushima Fukushima,Miuma Miuma,Haraguchi Haraguchi,Matsuzaki Matsuzaki,Miyaaki Miyaaki,Ooba Ooba,Nakao Nakao,Hidaka Hidaka,Hashimoto Hashimoto,Kinoshita Kinoshita,Eguchi Eguchi,Kugiyama Kugiyama,Yatsuhashi Yatsuhashi,Shigeno Shigeno,Tajima Tajima,Motoyoshi Motoyoshi,Matsuo Matsuo

doi:10.3390/cancers11111769

Abstract

Background: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. Methods: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. Results: Fourteen patients were Child–Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI ≥67.0% group, OS was significantly better than in the 8-week RDI <67.0% group (p = 0.003). Conclusions: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally [1,2,3,4]
Regarding the previous systemic chemotherapy, all 15 patients were treated with sorafenib
Lenvatinib pharmacokinetics in patients with HCC were affected by body weight, supporting a body weight-based dosing approach [18,19]

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally [1,2,3,4]. Multiple drugs, such as regorafenib [5], lenvatinib [6], ramucirumab [7], and cabozantinib [8] in addition to sorafenib [9,10], have been shown to be effective for HCC Of these molecular target agents, sorafenib and lenvatinib are currently available as the first-line treatment for advanced unresectable HCC [6,9,10]. The relationship between dosage and treatment effect in patients with HCC in clinical practice has not fully elucidated and remains unclear The purpose of this retrospective study was to evaluate the relationship between the RDI and the patients’ response to lenvatinib in clinical settings. There was a significant difference in RDI between the OR and non-OR groups (p < 0.05)

Methods

Results

Discussion

Conclusion