Atsushi Hiraoka1, Takashi Kumada2, Toshifumi Tada3, Kazuya Kariyama4, Joji Tani5, Shinya Fukunishi6, Masanori Atsukawa7, Masashi Hirooka8, Kunihiko Tsuji9, Toru Ishikawa10, Koichi Takaguchi11, Ei Itobayashi12, Kazuto Tajiri13, Noritomo Shimada14, Hiroshi Shibata15, Hironori Ochi16, Kazuhito Kawata17, Satoshi Yasuda18, Hidenori Toyoda18, Hideko Ohama6, Kazuhiro Nouso4, Akemi Tsutsui11, Takuya Nagano11, Norio Itokawa7, Korenobu Hayama7, Taeang Arai7, Michitaka Imai10, Yohei Koizumi8, Shinichiro Nakamura3, Kouji Joko16, Kojiro Michitaka1, Yoichi Hiasa8, Masatoshi Kudo19. 1. Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan. 2. Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 3. Department of Internal Medicine, Himeji Red Cross Hospital, Hyogo, Japan. 4. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 5. Department of Gastroenterology and Hepatology, Kagawa university, Kagawa, Japan. 6. Department of Gastroenterology, Osaka Medical College, Osaka, 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, Ehime, Japan. 9. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 10. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 11. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 12. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 13. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 14. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 15. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 16. Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan. 17. Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 18. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan. 19. Department of Gastroenterology, Kindai University, Osaka, Japan.
Abstract
BACKGROUND/AIM: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). METHODS: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. RESULTS: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). CONCLUSION: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.
BACKGROUND/AIM: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). METHODS: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. RESULTS: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). CONCLUSION: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245