Atsushi Hiraoka1, Takashi Kumada2, Takeshi Hatanaka3, Toshifumi Tada4, Kazuya Kariyama5, Joji Tani6, Shinya Fukunishi7, Masanori Atsukawa8, Masashi Hirooka9, Kunihiko Tsuji10, Toru Ishikawa11, Koichi Takaguchi12, Ei Itobayashi13, Kazuto Tajiri14, Noritomo Shimada15, Hiroshi Shibata16, Hironori Ochi17, Kazuhito Kawata18, Satoshi Yasuda19, Hidenori Toyoda19, Ogawa Chikara20, Tsutomu Tamai21, Satoru Kakizaki22,23, Hiroki Tojima22, Tamon Nagashima24, Takashi Ueno25, Daichi Takizawa26, Atsushi Naganuma27, Hideko Ohama7, Kazuhiro Nouso5, Akemi Tsutsui12, Takuya Nagano12, Norio Itokawa8, Tomomi Okubo8, Taeang Arai8, Michitaka Imai11, Yohei Koizumi9, Shinichiro Nakamura4, Kouji Joko17, Kojiro Michitaka1, Yoichi Hiasa9, Masatoshi Kudo28. 1. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan. 2. Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 3. Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan. 4. Department of Internal Medicine, Himeji Red Cross Hospital, Hyogo, Japan. 5. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 6. Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan. 7. Department of Gastroenterology, Osaka Medical College, Osaka, Japan. 8. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 9. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. 10. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 11. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 12. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 13. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 14. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 15. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 16. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 17. Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan. 18. Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 19. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan. 20. Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu, Japan. 21. Department of Gastroenterology, Kagoshima City Hospital, Kagoshima, Japan. 22. Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. 23. Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan. 24. Department of Gastroenterology, National Hospital Organization Shibukawa Medical Center, Takasaki, Japan. 25. Department of Internal Medicine, Isesaki Municipal Hospital, Isesaki, Gunma, Japan. 26. Department of Gastroenterology, Maebashi Red Cross Hospital, Maebashi, Japan. 27. Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan. 28. Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan.
Abstract
AIM: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure. METHODS: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting. RESULTS: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment. CONCLUSION: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.
AIM: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure. METHODS: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting. RESULTS: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment. CONCLUSION: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinomapatients with better hepatic reserve function.