Safety and Effectiveness of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice: An Observational Post-Marketing Study in Japan

Junji Furuse; Namiki Izumi; Kenta Motomura; Yoshitaka Inaba; Yoshio Katamura; Yasuteru Kondo; Kazuhisa Yabushita; Katsuaki Motoyoshi; Masatoshi Kudo

doi:10.1007/s40801-022-00348-w

Safety and Effectiveness of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice: An Observational Post-Marketing Study in Japan

Drugs Real World Outcomes. 2023 Jun;10(2):195-205. doi: 10.1007/s40801-022-00348-w. Epub 2023 Jan 5.

Authors

Junji Furuse¹, Namiki Izumi², Kenta Motomura³, Yoshitaka Inaba⁴, Yoshio Katamura⁵, Yasuteru Kondo⁶, Kazuhisa Yabushita⁷, Katsuaki Motoyoshi⁸, Masatoshi Kudo⁹

Affiliations

¹ Kanagawa Cancer Center, Kanagawa, Japan. junjifuruse@yahoo.co.jp.
² Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
³ Department of Hepatology, Aso Iizuka Hospital, Fukuoka, Japan.
⁴ Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Aichi, Japan.
⁵ Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan.
⁶ Department of Hepatology, Sendai Kousei Hospital, Miyagi, Japan.
⁷ Department of Internal Medicine, Fukuyama City Hospital, Hiroshima, Japan.
⁸ Eisai Co., Ltd., Tokyo, Japan.
⁹ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

Abstract

Background: Lenvatinib was approved for use in unresectable hepatocellular carcinoma (uHCC) in Japan in 2018. Patients with diverse clinical characteristics receive lenvatinib treatment in clinical practice. Thus, it is crucial to evaluate the safety and effectiveness of lenvatinib in real-world clinical settings.

Objective: This study aimed to evaluate the real-world safety and effectiveness of lenvatinib for uHCC in clinical practice in Japan.

Patients and methods: Between July 2018 and January 2019, patients with uHCC who were administered lenvatinib for the first time were enrolled in this prospective, multicenter, observational post-marketing study (NCT03663114). Patients were orally administered lenvatinib and followed up for 12 months. For safety, adverse drug reactions (ADRs) were evaluated. For effectiveness, the objective response rate (ORR) was calculated to evaluate tumor response. Overall survival (OS) was estimated using the Kaplan-Meier method.

Results: Data of 703 patients (median age, 73 years; 80.2% males) were analyzed. The median (range) treatment duration was 25.3 (0.3-68.9) weeks. The mean ± standard deviation initial dose was 7.37 ± 1.65 mg in patients with body weight < 60 kg and 10.43 ± 2.49 mg in those with body weight ≥ 60 kg. ADRs (any grade) were reported in 84.9% of the patients, with Grade ≥ 3 ADRs reported in 42.5% of the patients. The most common ADRs (> 10%) were decreased appetite, fatigue, hypertension, proteinuria, palmar-plantar erythrodysesthesia, hypothyroidism, and diarrhea. The median OS of the 703 patients was 498.0 days. In 494 patients assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the ORR was 39.5% (95% confidence interval: 35.1-43.9%). Patients with better liver or renal function at baseline achieved significantly higher ORR than those with worse liver or renal function.

Conclusions: In patients with uHCC in real-world clinical practice in Japan, treatment with lenvatinib was generally well tolerated, and no new safety concerns were identified. The ORR and median OS were similar to or better than the results of the Japanese subset of the global Phase III REFLECT trial. Our results demonstrated that clinically meaningful treatment responses were achieved with lenvatinib in real-world clinical practice.