Real-World Data on Ramucirumab Therapy including Patients Who Experienced Two or More Systemic Treatments: A Multicenter Study

Cancers - Tập 14 Số 12 - Trang 2975
Yutaka Yasui1, Masayuki Kurosaki1, Kaoru Tsuchiya1, Yuka Hayakawa1, Chitomi Hasebe2, Masami Abe2, Chikara Ogawa3, Kouji Joko4, Hironori Ochi4, Toshifumi Tada5, Kazuhiro Nouso5, Koichiro Furuta6, Hiroyuki Kimura7, Keiji Tsuji8, Yuji Kojima9, Takehiro Akahane10, Takashi Tamada11, Yasushi Uchida12, Masahiko Kondo13, Akeri Mitsuda14, Namiki Izumi
1Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan
2Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa 070-8530, Japan
3Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu 760-0017, Japan
4Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
5Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji 670-8540, Japan
6Department of Internal Medicine, Masuda Red Cross Hospital, Masuda 698-8501, Japan
7Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto 605-0981, Japan
8Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima 730-8619, Japan
9Department of Gastroenterology, Japanese Red Cross Ise Hospital, Ise 516-8512, Japan
10Department of Gastroenterology, Ishinomaki Red Cross Hospital, Ishinomaki 986-8522, Japan
11Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki 569-1096, Japan
12Department of Gastroenterology, Matsue Red Cross Hospital, Matsue 690-8506, Japan
13Department of Gastroenterology, Otsu Red Cross Hospital, Otsu 520-8511, Japan
14Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori 680-8517, Japan

Tóm tắt

Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC.

Từ khóa


Tài liệu tham khảo

Faivre, 2020, Molecular therapies for HCC: Looking outside the box, J. Hepatol., 72, 342, 10.1016/j.jhep.2019.09.010

Finn, 2020, Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma, N. Engl. J. Med., 382, 1894, 10.1056/NEJMoa1915745

Rimassa, 2020, Navigating the new landscape of second-line treatment in advanced hepatocellular carcinoma, Liver Int., 40, 1800, 10.1111/liv.14533

Zhu, 2015, Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): A randomised, double-blind, multicentre, phase 3 trial, Lancet Oncol., 16, 859, 10.1016/S1470-2045(15)00050-9

Zhu, 2019, Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): A randomised, double-blind, placebo-controlled, phase 3 trial, Lancet Oncol., 20, 282, 10.1016/S1470-2045(18)30937-9

Sonbol, 2020, Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis, JAMA Oncol., 6, e204930, 10.1001/jamaoncol.2020.4930

Llovet, 2008, Sorafenib in advanced hepatocellular carcinoma, N. Engl. J. Med., 359, 378, 10.1056/NEJMoa0708857

Kudo, 2018, Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial, Lancet, 391, 1163, 10.1016/S0140-6736(18)30207-1

Bruix, 2017, Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial, Lancet, 389, 56, 10.1016/S0140-6736(16)32453-9

Meyer, 2018, Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma, N. Engl. J. Med., 379, 54, 10.1056/NEJMoa1717002

Kudo, 2021, Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2, JHEP Rep., 3, 100215, 10.1016/j.jhepr.2020.100215

Ogushi, 2020, Safety and Efficacy of Lenvatinib Treatment in Child-Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis, Clin. Exp. Gastroenterol., 13, 385, 10.2147/CEG.S256691

Maruta, 2020, Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma, Liver Cancer, 9, 382, 10.1159/000507022

Sho, 2020, Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria, Hepatol. Res., 50, 966, 10.1111/hepr.13511

Tsuchiya, K., Kurosaki, M., Sakamoto, A., Marusawa, H., Kojima, Y., Hasebe, C., Arai, H., Joko, K., Kondo, M., and Tsuji, K. (2021). The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study. Cancers, 13.

Kirino, S., Tsuchiya, K., Kurosaki, M., Kaneko, S., Inada, K., Yamashita, K., Osawa, L., Hayakawa, Y., Sekiguchi, S., and Okada, M. (2020). Relative dose intensity over the first four weeks of lenvatinib therapy is a factor of favorable response and overall survival in patients with unresectable hepatocellular carcinoma. PLoS ONE, 15.

Eisenhauer, 2009, New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1), Eur. J. Cancer, 45, 228, 10.1016/j.ejca.2008.10.026

Kanda, 2013, Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics, Bone Marrow Transplant., 48, 452, 10.1038/bmt.2012.244

Takeda, 2019, Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion, Hepatol. Res., 49, 594, 10.1111/hepr.13294

Hatanaka, 2020, Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study, Hepatol. Res., 50, 382, 10.1111/hepr.13460

Chuma, 2021, Analysis of efficacy of lenvatinib treatment in highly advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein or tumor with more than 50% liver occupation: A multicenter analysis, Hepatol. Res., 51, 201, 10.1111/hepr.13592

Hiraoka, 2021, Therapeutic efficacy of lenvatinib as third line treatment following regorafenib for unresectable hepatocellular carcinoma progression, Hepatol. Res., 51, 880, 10.1111/hepr.13644

Tomonari, 2021, Comparison of therapeutic outcomes of sorafenib and lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular-targeted agent sequential therapy: A propensity score-matched analysis, Hepatol. Res., 51, 472, 10.1111/hepr.13597

Kuzuya, 2020, Initial Experience of Ramucirumab Treatment After Lenvatinib Failure for Patients With Advanced Hepatocellular Carcinoma, Anticancer Res., 40, 2089, 10.21873/anticanres.14167

Hiraoka, 2021, Therapeutic efficacy of ramucirumab after lenvatinib for post-progression treatment of unresectable hepatocellular carcinoma, Gastroenterol. Rep., 9, 133, 10.1093/gastro/goaa042

Kasuya, 2021, Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib, Intern. Med., 60, 345, 10.2169/internalmedicine.5185-20

Kudo, 2020, Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2, Liver Int., 40, 2008, 10.1111/liv.14462

Kudo, 2017, Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial, J. Gastroenterol., 52, 494, 10.1007/s00535-016-1247-4

Kudo, 2020, Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial, J. Gastroenterol., 55, 627, 10.1007/s00535-020-01668-w

Zhu, 2017, Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score, JAMA Oncol., 3, 235, 10.1001/jamaoncol.2016.4115

Kaneko, 2020, Strategy for advanced hepatocellular carcinoma based on liver function and portal vein tumor thrombosis, Hepatol. Res., 50, 1375, 10.1111/hepr.13567

Terashima, 2020, Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma, Hepatol. Res., 50, 871, 10.1111/hepr.13505

Uchikawa, 2018, Clinical outcomes of sorafenib treatment failure for advanced hepatocellular carcinoma and candidates for regorafenib treatment in real-world practice, Hepatol. Res., 48, 814, 10.1111/hepr.13180

Kuzuya, 2019, Clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment, Hepatol. Res., 49, 1054, 10.1111/hepr.13358

Kudo, 2021, Ramucirumab in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Outcomes by treatment-emergent ascites, Hepatol. Res., 51, 715, 10.1111/hepr.13638

Thông tin
Thông tin xuất bản

Cancers

Tập 14 Số 12

2975

Thông tin tác giả