Early response and safety of L e n v a t i n i b f or patients with advanced hepatocellular carcinoma in a real - world setting T. Sho1, G. Suda1, T. Shigesawa1, K. Suzuki1, A. Nakamura1, M. Ohara1, N. Kawagishi1, M. Nakai1, M. Natusizaka1, K. Morikawa1, K. Ogawa1, M. Baba2, K. Furuya2, Y. Yamamoto3, T. Kobayashi4, T. Meguro5, A. Saga6, T. Miyagishima7, H. Yokoo8, T. Kamiyama8,A. Taketomi8, N. Sakamoto1 1Department of Gastroenterology and Hepatology, University Graduate School of Medicine, Hokkaido, Japan. 2JCHO Hokkaido Hospital, Gastroenterology and Hepatology, Japan. 3Hakodate City Hospital, Gastroenterology, Japan. 4Tomakomai City Hospital, Gastroenterology, Japan. 5Hokkaido Gastroenterology Hospital, Japan 6Kaisei Hospital, Japan. 7Kushiro Rosai Hospital, Japan. 8 Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Japan

1 INTRODUCTION 4 RESULTS 5 CONCLUSIONS The phase 3 trial REFLECT [1] was the Table 1. Baseline patient characteristics Table 2. Clinical response to lenvatinib ⚫ This real-world study revealed that Met the Did not met the Met the Did not meet the Overall cohort first to showed that the OS of patients Overall cohort REFLECT REFLECT Response REFLECT criteria REFLECT criteria p value Clinical characteristics P value (n=41) lenvatinib yields high early response rate with advanced HCC who were treated (n=41) criteria criteria (n=18) (n=23)

(n=18) (n=23) Complete response, n (%) 5 (12.2%) 2 (11.1%) 3 (13.0%) and tolerability for advanced HCC. at: presented Poster with lenvatinib is non-inferior to that of Age, years 71 (46-97) 75 (46-83) 70 (54-97) 0.1026 Partial response, n (%) 20 (48.8%) 9 (50.0%) 11 (47.8%) treated with sorafenib. Sex Stable disease, n (%) 12 (29.3%) 5 (27.8%) 7 (30.4%) ⚫ Favorable outcomes were similarly Male 37 18 19 0.0259 Progressive disease, n (%) 4 (9.8%) 2 (11.1%) 2 (8.7%) The progression-free survival of patients Female 4 0 4 observed even in patients who did not meet treated with lenvatinib was significantly Etiology Objective response rate 61.0% (25/41) 61.1% (11/18) 60.9% (14/23) 0.8293 the REFLECT inclusion criteria. HBV 14 3 11 0.0311 Disease control rate 90.2% (37/41) 88.9% (16/18) 91.3% (21/23) 0.7965 longer than that of treated with sorafenib. HCV 7 2 5 The efficacy and safety of for the Others 20 13 7 patients who did not met the inclusion ECOG PS Table 3. Adverse events and treatment discontinuations 0 28 11 17 Met the Did not meet the 6 ACKNOWLEDGEMENTS 0.3003 Overall cohort criteria of the REFLECT are not clarified. 1 12 7 5 REFLECT criteria REFLECT criteria p value (n=41) The authors would like to thank all patients and their families as well as 2 1 0 1 (n=18) (n=23) In addition, real-world data have also 4 theinvestigators and staff of the participating institutions, NORTE study Platelet, ×10 /uL 13.8 (4.4-33.6) 14.7 (8.5-25.8) 13.6 (4.4-33.6) 0.6176 Treatment 3 (7.3%) 1 (5.6%) 2 (8.7%) 0.6982 group. The principal investigators of the NORTE study sites are listed been quite limited. NH3, µg/dl 41 (13-118) 35 (18-76) 43 (13-118) 0.1565 discontinuation Albumin, g/dl 3.7 (2.8-4.5) 3.8 (3.0-4.5) 3.5 (2.8-4.3) 0.0615 Interruption and/or below: 30 (73.2%) 15 (83.3%) 15 (65.2%) 0.1860 DOI: 10.3252/pso.eu.ILC2019.2019 Total bilirubin, mg/dl 0.7 (0.2-3.1) 0.7 (0.2-2.1) 0.7 (0.3-3.1) 0.6535 dose reduction J. Yoshida(JCHO Hokushin Hospital), A. Nagasaka (Sapporo ALBI grade Worsened Child City General Hospital), A. Fujinaga (-Kosei General Hospital), 18 (43.4%) 8 (44.4%) 10 (43.5%) 0.9507 2 AIM 1 12 6 6 0.6135 Pugh score H. Kikuchi, T. Atarashi (-Kosei General Hospital), K. Furuya 2 29 12 17 (JCHO HokkaidoHospital), S. Muto (National Hospital Organization In this study, we aimed to evaluate the Child-Pugh score Adverse events Any grade Grade >3 Any grade Grade >3 Any grade Grade >3 Hokkaido Medical Center),T. Meguro (Hokkaido Gastroenterology 5 22 13 9 early therapeutic response of lenvatinib 0.0165 HFS 23 (56.1%) 6 (14.6%) 12 (66.7%) 3 (16.7%) 11 (47.8%) 3 (13.0%) Hospital), A. Saga (Kaisei Hospital), M. Okamoto (Aiiku Hospital), M. 6 14 5 9 General fatigue 24 (58.5%) 0 (0%) 13 (72.2%) 0 (0%) 11 (47.8%) 0 (0%) Katagiri (Sapporo Hokuyu Hospital), T. Miyagishima ( Rosai for patients with unresectable HCC in the 7-9 5 0 5 Appetite loss 28 (68.3%) 1 (2.4%) 14 (77.8%) 1 (5.6%) 14 (60.9%) 0 (0%) Hospital), J. Konno (HakodateCentral General Hospital), K. Kumagai 15.4 5.8 52.3 real-world setting, focusing on patients AFP, ng/ml 0.0444 DiarrheaA 9 (22.0%) 1 (2.4%) 3 (16.7%) 1 (5.6%) 6 (26.1%) 0 (0%) (Mori city National Health Insurance Hospital), M. Onodera (NTT EAST (1.6-449909.0) (2.0-19394.3) (1.6-449909.0) Hypertension 28 (68.3%) 5 (12.2%) 15 (83.3%) 2 (11.1%) 13 (56.5%) 3 (13.3%) Sapporo Hospital), T. Kobayashi ( City Hospital), 734 384 1409 who did not meet the inclusion criteria of DCP, mAU/ml 0.1458 Hepatic coma 3 (7.3%) 3 (7.3%) 1 (5.6%) 1 (5.6%) 2 (8.7%) 2 (8.7%) M. Uebayashi (Japanese Red Cross Hospital), K. Katou (12-43200) (15043200) (13-27425) Weight loss 6 (14.6%) 0 (0%) 5 (27.8%) 0 (0%) 1 (4.3%) 0 (0%) the REFLECT trial but did not have a Maximum intrahepatic tumor (Iwamizawa Municipal General Hospital), Y. Kunieda ( City 37 (8-135) 41 (10-123) 36 (8-135) 0.6254 Urine protein 23 (56.1%) 1 (2.4%) 11 (61.1%) 1 (5.6%) 12 (52.2%) 0 (0%) Hospital), M. Tateyama (Tomakomai Nissho Hospital), A. Kawakami contraindication according to the package size, mm Decreased platelets 21 (51.2%) 5 (12.2%) 10 (55.6%) 2 (11.1%) 11 (47.8%) 3 (13.0%) (Sapporo Century Hospital), Tsunematsu (Touei hospital), K. Shinada BCLC stage Hypothyroidism 21 (51.2%) 0 (0%) 11 (61.1%) 0 (0%) 10 (43.5%) 0 (0%) insert of lenvatinib. (Keiwakai Hospital) and Yoshiya Ymamoto ( City B 14 6 8 0.9226 Dysgeusia 3 (7.3%) 0 (0%) 1 (5.6%) 0 (0%) 2 (8.7%) 0 (0%) C 27 12 15 Rush 1 (2.4%) 1 (2.4%) 1 (5.6%) 1 (5.6%) 0 (0%) 0 (0%) General Hospital) Positive for Vp 10 (24.4%) 4 (22.2%) 6 (26.1%) 0.8532 Decreased albumin 21 (51.2%) 0 (0%) 9 (50.0%) 0 (0%) 12 (52.2%) 0 (0%) Vp3 6 2 4 Increased bilirubin 8 (19.5%) 1 (2.4%) 4 (22.2%) 1 (5.6%) 4 (17.4%) 1 (4.3%) 3 METHOD Vp4 0 0 0 Ascites 5 (12.2%) 0 (0%) 1 (5.6%) 0 (0%) 4 (17.4%) 0 (0%) 7 Positive for Vv 2 (4.9%) 2 (11.1%) 0 (0%) 0.0642 Hyperthyroidism 1 (2.4%) 0 (0%) 1 (5.6%) 0 (0%) 0 (0%) 0 (0%) REFERENCES In patients who were administered Positive for bile duct invasion 4 (9.8%) 0 (0%) 4 (17.4%) 0.0259 Increased creatinine 4 (9.8%) 0 (0%) 2 (11.1%) 0 (0%) 2 (8.7%) 0 (0%) Positive for LN metastasis 5 (12.2%) 2 (11.1%) 3 (13.0%) 0.8507 1. Kudo M et al. Lenvatinib versus sorafenib in first-line lenvatinib for advanced HCC between Positive for EHM 10 (24.4%) 4 (22.2%) 6 (26.1%) 0.7743 treatment of patients with unresectable hepatocellular April and October 2018, patients who Naïve: recurrence 7:36 3:15 2:21 0.1500 100,0% 100,0% History of operation 16 (39.0%) 6 (33.3%) 10 (43.5%) 0.5074 A B carcinoma: a randomised phase 3 non-inferiority 80,0% 50,0% were followed for more than 2 months, History of RFA 11 (26.8%) 5 (27.8%) 6 (26.1%) 0.9036 trial.Lancet. 2018, 24;1163-1173 60,0% and were evaluated the treatment History of TACE 30 (73.2%) 13 (72.2%) 17 (73.9%) 0.9036 0,0% <0.000 History of Sorafenib 16 (39.0%) 0 (0%) 16 (69.6%) 40,0% response via dynamic computed 1 -50,0% 20,0% 8 CONTACT tomography at baseline and 2 months History of Regorafenib 4 (9.8) 0 (0%) 4 (17.4%) 0.0259 -100,0% 0,0% after treatment initiation were enrolled. Corresponding author : Takuya Sho, MD, PhD. Liver tumours Takuya Sho -20,0% 100,0% Further analysis by stratifying patients Fig. 1 Waterfall plot of changes in targeted tumor size as assessed C Department of Gastroenterology and Hepatology, Hokkaido -40,0% 50,0% according to compliance and non- according to mRECIST. University Faculty of Medicine and Graduate School of Medicine. A. Overall patient cohort. -60,0% 0,0% Kita 15, Nishi 7, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan compliance with the REFLECT inclusion B. In patients who meet the REFLECT inclusion criteria. -80,0% -50,0% Phone +81-11-706-7715, Fax +81-11-706-7867 C. In patients who did meet the REFLECT inclusion criteria. criteria was conducted. -100,0% -100,0% E-mail : [email protected]

FRI-505

ILC2019