Ilario Giovanni Rapposelli1, Toshifumi Tada2, Shigeo Shimose3, Valentina Burgio4, Takashi Kumada5, Hideki Iwamoto3, Atsushi Hiraoka6, Takashi Niizeki3, Masanori Atsukawa7, Hironori Koga3, Masashi Hirooka8, Takuji Torimura3, Massimo Iavarone9, Raffaella Tortora10, Claudia Campani11, Sara Lonardi12,13, Emiliano Tamburini14, Fabio Piscaglia15, Gianluca Masi16, Giuseppe Cabibbo17, Francesco Giuseppe Foschi18, Marianna Silletta19, Kunihiko Tsuji20, Toru Ishikawa21, Koichi Takaguchi22, Kazuya Kariyama23, Ei Itobayashi24, Kazuto Tajiri25, Noritomo Shimada26, Hiroshi Shibata27, Hironori Ochi28, Satoshi Yasuda29, Hidenori Toyoda29, Shinya Fukunishi30, Hideko Ohama30, Kazuhito Kawata31, Joji Tani32, Shinichiro Nakamura2, Kazuhiro Nouso23, Akemi Tsutsui22, Takuya Nagano22, Takaaki Tanaka6, Norio Itokawa7, Tomomi Okubo7, Taeang Arai7, Michitaka Imai21, Kouji Joko28, Yohei Koizumi8, Yoichi Hiasa8, Margherita Rimini33, Francesca Ratti34, Luca Aldrighetti34, Stefano Cascinu4,35, Andrea Casadei-Gardini4,35. 1. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST, Meldola, Italy. 2. Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan. 3. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. 4. Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy. 5. Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 6. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 8. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan. 9. Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. 10. Liver Unit, Cardarelli Hospital, Naples, Italy. 11. Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. 12. Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. 13. Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. 14. Department of Medical Oncology, Card. G. Panico Hospital of Tricase, Tricase, Italy. 15. Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Azienda Ospedaliero Universitaria di Bologna, Italy. 16. Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 17. Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy. 18. Department of Internal Medicine, Faenza Hospital, AUSL Romagna, Faenza, Italy. 19. Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy. 20. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 21. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 22. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 23. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 24. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 25. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 26. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 27. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 28. Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan. 29. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 30. Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. 31. Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. 32. Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan. 33. Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. 34. Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, Italy. 35. Vita-Salute San Raffaele University, Milan, Italy.
Abstract
BACKGROUND AND AIM: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. METHODS: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). RESULTS: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277). CONCLUSIONS: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.
BACKGROUND AND AIM: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. METHODS: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). RESULTS: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277). CONCLUSIONS: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.