臨床外科78巻1号

2023年01月発行

特集 外科医が知っておくべき！ 免疫チェックポイント阻害薬 各論

胆道癌・膵癌における免疫チェックポイント阻害薬の臨床試験および今後の展望

著者： 手塚瞬¹ 上野誠¹ 古瀬純司¹

所属機関： ¹神奈川県立がんセンター消化器内科

ページ範囲：P.56 - P.60

【ポイント】
◆2022年11月時点において，MSI-HighまたはTMB-Highを有する患者を除き，胆道癌および膵癌患者に対する免疫チェックポイント阻害薬の投与は本邦で薬事承認されていない．
◆治癒切除不能な胆道癌患者を対象とした国際共同第Ⅲ相試験であるTOPAZ-1試験において，ゲムシタビンとシスプラチンとの併用への抗PD-L1抗体薬デュルマルマブの上乗せの有効性および安全性が示された．

参考文献

targeting immune checkpoint molecules. J Hepatol 71：753-762, 2019

2）Sabbatino F, Villani V, Yearley JH, et al：PD-L1 and HLA class Ⅰ antigen expression and clinical course of the disease in intrahepatic cholangiocarcinoma. Clin Cancer Res 22：470-478, 2016

3）Kim R, Coppola D, Wang E, et al：Prognostic value of CD8CD45RO tumor infiltrating lymphocytes in patients with extrahepatic cholangiocarcinoma. Oncotarget 9：23366-23372, 2018

4）Fluxa P, Rojas-Sepulveda D, Gleisner MA, et al：High CD8（＋） and absence of Foxp3（＋） T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival. BMC Cancer 18：243, 2018

5）Ueno M, Ikeda M, Morizane C, et al：Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer：a non-randomised, multicentre, open-label, phase 1 study. Lancet Gastroenterol Hepatol 4：611-621, 2019

6）Kim RD, Chung V, Alese OB, et al：A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol 6：888-894, 2020

7）Yoo C, Oh DY, Choi HJ, et al：Phase Ⅰ study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer 8：e000564, 2020

8）Merck Reports Topline Data for Bintrafusp Alfa as Second-Line Monotherapy Treatment in Biliary Tract Cancer. 16 March, 2021　https://www.merckgroup.com/en/news/bintrafusp-topline-data-biliary-tract-cancer-16-03-2021.html

9）Piha-Paul SA, Oh DY, Ueno M, et al：Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer：Results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer 147：2190-2198, 2020

10）Doki Y, Ueno M, Hsu CH, et al：Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer. Cancer Med 11：2550-2560, 2022

11）Klein O, Kee D, Nagrial A, et al：Evaluation of combination nivolumab and ipilimumab immunotherapy in patients with advanced biliary tract cancers：subgroup analysis of a phase 2 nonrandomized clinical trial. JAMA Oncol 6：1405-1049, 2020

12）U.S. National Library of Medicine：Gemcitabine plus cisplatin with or without bintrafusp alfa（M7824） in participants with 1LBTC. 26 Aug, 2019　https://clinicaltrials.gov/ct2/show/results/NCT04066491

13）Oh DY, He AR, Qin S, et al：Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid 1：EVIDoa2200015, 2022

14）Lamarca A, Hubner RA, David Ryder W, et al：Second-line chemotherapy in advanced biliary cancer：a systematic review. Ann Oncol 25：2328-2338, 2014

15）Merck Statement on Phase Ⅱ Study of Bintrafusp Alfa in First-Line Treatment of Biliary Tract Cancer. 23 Aug, 2021　https://www.merckgroup.com/en/news/bintrafusp-alfa-update-23-08-2021.html

16）Balachandran VP, Beatty GL, Dougan SK：Broadening the impact of immunotherapy to pancreatic cancer：challenges and opportunities. Gastroenterology 156：2056-2072, 2019

17）Royal RE, Levy C, Turner K, et al：Phase 2 trial of single agent Ipilimumab（anti-CTLA-4）for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 33：828-833, 2010

18）Brahmer JR, Tykodi SS, Chow LQ, et al：Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366：2455-2465, 2012

19）Kamath SD, Kalyan A, Kircher S, et al：Ipilimumab and gemcitabine for advanced pancreatic cancer：a phase Ⅰb study. Oncologist 25：e808-e815, 2020

20）Weiss GJ, Blaydorn L, Beck J, et al：Phase Ⅰb/Ⅱ study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs 36：96-102, 2018

21）Wainberg ZA, Hochster HS, Kim EJ, et al：Open-label, phase Ⅰ study of nivolumab combined with nab-paclitaxel plus gemcitabine in advanced pancreatic cancer. Clin Cancer Res 26：4814-4822, 2020

22）Ueno M, Morizane C, Ikeda M, et al：A phase Ⅱ study of nivolumab in combination with modified FOLFIRINOX for metastatic pancreatic cancer. J Clin Oncol 40（4 suppl）：553, 2022