臨床外科79巻7号

2024年07月発行

特集 外科医が知っておくべき 肝胆膵腫瘍に対する薬物療法

肝臓

切除不能肝細胞癌に対する薬物療法

著者： 赤星径一¹ 田邉稔¹

所属機関： ¹東京医科歯科大学医学部肝胆膵外科学分野

ページ範囲：P.720 - P.725

文献概要

【ポイント】
◆切除不能肝細胞癌に対する薬物療法は2018年以降大きく進歩し，特に免疫チェックポイント阻害薬の登場がトピックである．
◆薬物療法と局所療法（手術，TACE，RFA）の組み合わせ治療の有用性が期待され，議論が活性化している．
◆腫瘍学的見地からの手術適応判断の議論を円滑化するためにOncological resectability criteriaが提唱された．

参考文献

1）Llovet JM, Ricci S, Mazzaferro V, et al：Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359：378-390, 2008

2）Cheng AL, Kang YK, Chen Z, et al：Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma：a phase Ⅲ randomised, double-blind, placebo-controlled trial. Lancet Oncol 10：25-34, 2009

3）Cheng AL, Kang YK, Lin DY, et al：Sunitinib versus sorafenib in advanced hepatocellular cancer：results of a randomized phase Ⅲ trial. J Clin Oncol 31：4067-4075, 2013

4）Johnson PJ, Qin S, Park JW, et al：Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma：results from the randomized phaseⅢ BRISK-FL study. J Clin Oncol 31：3517-3524, 2013

5）Kudo M, Finn RS, Qin S, et al：Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma：a randomised phase 3 non-inferiority trial. Lancet 391：1163-1173, 2018

6）Finn RS, Qin S, Ikeda M, et al：Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 382：1894-1905, 2020

7）Cheng AL, Qin S, Ikeda M, et al：Updated efficacy and safety data from IMbrave150：Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol 76：862-873, 2022

8）Abou-Alfa GK, Lau G, Kudo M, et al：Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid 1：EVIDoa2100070, 2022

9）Bruix J, Qin S, Merle P, et al：RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment（RESORCE）：a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389：56-66, 2017

10）Zhu AX, Kang YK, Yen CJ, et al：Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations（REACH-2）：a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20：282-296, 2019

11）Abou-Alfa GK, Meyer T, Cheng AL, et al：Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 379：54-63, 2018

12）日本肝臓学会（編）；肝癌診療ガイドライン2017年版補訂版．金原出版，2020

13）Reig M, Forner A, Rimola J, et al：BCLC strategy for prognosis prediction and treatment recommendation：The 2022 update. J Hepatol 76：681-693, 2022

14）Forner A, Reig M, Bruix J：Hepatocellular carcinoma. Lancet 391：1301-1314, 2018

15）日本肝臓学会（編）；肝癌診療ガイドライン2021年版．金原出版，2021

16）Asaoka Y, Tateishi R, Yamada Y, et al：Real world data of systemic therapy for hepatocellular carcinoma in Japan：HERITAGE study. J Clin Oncol 41：510, 2023

17）Kudo M, Ueshima K, Saeki I, et al：A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma：TACTICS-L Trial. Liver Cancer 13：99-112, 2023

18）Ichida A, Arita J, Hatano E, et al：A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma（LENS-HCC Trial）. Liver Cancer, 2023

19）Okuno M, Ishii T, Ichida A, et al：Protocol of the RACB study：a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab. BMC Cancer 23：780, 2023

20）Ban D, Ogura T, Akahoshi K, et al：Current topics in the surgical treatments for hepatocellular carcinoma. Ann Gastroenterol Surg 2：137-146, 2018

21）Hasegawa K, Takemura N, Yamashita T, et al：Clinical Practice Guidelines for Hepatocellular Carcinoma：The Japan Society of Hepatology 2021 version（5th JSH-HCC Guidelines）. Hepatol Res 53：383-390, 2023

22）Akahoshi K, Shindoh J, Tanabe M, et al：Questionnaire survey of Japanese board-certified expert hepatobiliary and pancreatic surgeons and instructors on the surgical indications for hepatocellular carcinoma. J Hepatobiliary Pancreat Sci 31：143-151, 2024

23）borderline resectable HCC WG：日本肝癌研究会・日本肝胆膵外科学会合同プロジェクト「いわゆるborderline resectable HCCに関するWG Expert Panel」成果報告書〔https://www.jshbps.jp/modules/project/index.php?content_id=18〕

24）Akahoshi K, Shindoh J, Tanabe M, et al：Oncological Resectability Criteria for Hepatocellular Carcinoma in the Era of Novel Systemic Therapies：the JLCA and JSHBPS Expert Consensus Statement 2023. Liver Cancer, 2024, DOI：10. 1159/000538627