Atsushi Hiraoka1, Takashi Kumada2, Shinya Fukunishi3, Masanori Atsukawa4, Masashi Hirooka5, Kunihiko Tsuji6, Toru Ishikawa7, Koichi Takaguchi8, Kazuya Kariyama9, Ei Itobayashi10, Kazuto Tajiri11, Noritomo Shimada12, Hiroshi Shibata13, Hironori Ochi14, Toshifumi Tada2, Hidenori Toyoda2, Keisuke Yokohama3, Kazuhiro Nouso9, Akemi Tsutsui8, Takuya Nagano8, Norio Itokawa4, Korenobu Hayama4, Taeang Arai4, Michitaka Imai7, Kouji Joko14, Yohei Koizumi5, Yoichi Hiasa5, Kojiro Michitaka1, Masatoshi Kudo15. 1. aGastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan. 2. bDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan. 3. cDepartment of Gastroenterology, Osaka Medical School, Osaka, Japan. 4. dDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 5. eDepartment of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. 6. fCenter of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 7. gDepartment of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 8. hDepartment of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 9. iDepartment of Gastroenterology, Okayama City Hospital, Okayama, Japan. 10. jDepartment of Gastroenterology, Asahi General Hospital, Asahi, Japan. 11. kDepartment of Gastroenterology, Toyama University Hospital, Toyama, Japan. 12. lDivision of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 13. mDepartment of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 14. nHepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan. 15. oDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Abstract
BACKGROUND/AIM: Post-progression treatment following tyrosine-kinase inhibitor (TKI) failure in patients with unresectable hepatocellular carcinoma (u-HCC) is important to prolong post-progression survival (PPS), which has a good correlation with overall survival (OS). This study aimed to elucidate the clinical features of progressive disease (PD) in patients treated with lenvatinib (LEN). MATERIALS/ METHODS: From March 2018 to June 2019, 156 u-HCC patients with Child-Pugh A were enrolled (median age: 71 years, Child-Pugh score 5:6 = 105:51, BCLC A:B:C = 8:56:92, modified albumin-bilirubin grade (mALBI) 1:2a:2b = 59:42:55, past history of sorafenib:regorafenib = 57:17). Clinical features were retrospectively evaluated. RESULTS: The median observation period was 8.5 months. Median OS was not obtained, while median time to decline to Child-Pugh B (CPB) was 11.4 months, median time to progression (TTP) was 8.4 months, and the period of LEN administration was 7.3 months. When we compared predictive values for time to decline to CPB based on Child-Pugh score and mALBI, values for Akaike information criterion (AIC) score and c-index of mALBI were superior as compared to Child-Pugh score (AIC: 592.3 vs. 599.7) (c-index: 0.655 vs. 0.597). Of the 73 patients with PD, 32 (43.8%) showed no decline to CPB or death. After excluding 3 without alpha-fetoprotein data at PD determination, only 14 (20.0%) of 70 showed REACH-2 eligibility. Non-mALBI 1/2a at the start of LEN was a significant risk factor for decline to CPB during LEN treatment (HR 2.552, 95% CI: 1.577-4.129; p < 0.001). CONCLUSION: Introduction of TKI therapy including LEN for u-HCC patients with better hepatic function (mALBI 1/2a: ALBI score ≤-2.27), when possible, increases the chance of undergoing post-progression treatment, which can improve PPS.
BACKGROUND/AIM: Post-progression treatment following tyrosine-kinase inhibitor (TKI) failure in patients with unresectable hepatocellular carcinoma (u-HCC) is important to prolong post-progression survival (PPS), which has a good correlation with overall survival (OS). This study aimed to elucidate the clinical features of progressive disease (PD) in patients treated with lenvatinib (LEN). MATERIALS/ METHODS: From March 2018 to June 2019, 156 u-HCC patients with Child-Pugh A were enrolled (median age: 71 years, Child-Pugh score 5:6 = 105:51, BCLC A:B:C = 8:56:92, modified albumin-bilirubin grade (mALBI) 1:2a:2b = 59:42:55, past history of sorafenib:regorafenib = 57:17). Clinical features were retrospectively evaluated. RESULTS: The median observation period was 8.5 months. Median OS was not obtained, while median time to decline to Child-Pugh B (CPB) was 11.4 months, median time to progression (TTP) was 8.4 months, and the period of LEN administration was 7.3 months. When we compared predictive values for time to decline to CPB based on Child-Pugh score and mALBI, values for Akaike information criterion (AIC) score and c-index of mALBI were superior as compared to Child-Pugh score (AIC: 592.3 vs. 599.7) (c-index: 0.655 vs. 0.597). Of the 73 patients with PD, 32 (43.8%) showed no decline to CPB or death. After excluding 3 without alpha-fetoprotein data at PD determination, only 14 (20.0%) of 70 showed REACH-2 eligibility. Non-mALBI 1/2a at the start of LEN was a significant risk factor for decline to CPB during LEN treatment (HR 2.552, 95% CI: 1.577-4.129; p < 0.001). CONCLUSION: Introduction of TKI therapy including LEN for u-HCC patients with better hepatic function (mALBI 1/2a: ALBI score ≤-2.27), when possible, increases the chance of undergoing post-progression treatment, which can improve PPS.
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