Safety and Efficacy of Lenvatinib Treatment in Child–Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis

Katsuaki Ogushi,1,* Makoto Chuma,1,* Haruki Uojima,2 Hisashi Hidaka,2 Kazushi Numata,1 Satoshi Kobayashi,3 Shunji Hirose,4 Nobuhiro Hattori,5 Tomoaki Fujikawa,6 Takahide Nakazawa,2 Naohisa Wada,2 Shuitirou Iwasaki,2 Taito Fukushima,3 Yusuke Sano,3 Makoto Ueno,3 Kuniyuki Kawano,3 Kota Tsuruya,4 Masako Shomura,4 Tsunamasa Watanabe,5 Kotaro Matsunaga,5 Yosuke Kunishi,7 Yusuke Saigusa,8 Kuniyasu Irie,9 Shogo Iwabuchi,6 Makoto Kako,10 Manabu Morimoto,3 Tatehiro Kagawa,4 Katsuaki Tanaka,11 Shin Maeda9 1Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan; 3Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; 6Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan; 7Department of Gastroenterology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan; 8Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 9Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan; 10Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan; 11Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan*These authors contributed equally to this workCorrespondence: Makoto Chuma Gastroenterological CenterYokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa 2320024, JapanTel +81 45 261 5656Fax +81 45 253 9955Email chuma@yokohama-cu.ac.jpPurpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P < 0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥ 0.7 vs < 0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5– 7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.Keywords: lenvatinib, tyrosine kinase inhibitor, hepatocellular carcinoma, Child-Pugh, adverse events, overall survival