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 胆道・膵臓

膵癌・胆道癌に対する分子標的薬治療の進歩

著者： 志村充広¹ 青木修一¹ 海野倫明¹

所属機関： ¹東北大学大学院消化器外科学分野

ページ範囲：P.779 - P.784

【ポイント】
◆がんゲノム解析により，膵癌・胆道癌の遺伝子プロファイリングを把握し，新規治療ターゲットを探索できる新時代に突入した．
◆新規分子標的薬の革新が膵癌・胆道癌における二次，三次までの治療戦略を可能にした．
◆全身化学療法，根治的切除，分子標的薬などを適切なタイミングで適切な患者に提供するエビデンスを集積する必要がある．

参考文献

1）Siegel RL, Miller KD, Wagle NS, et al：Cancer statistics, 2023. CA Cancer J Clin 73：17-48, 2023

2）Motoi F, Kosuge T, Ueno H, et al：Randomized phase Ⅱ/Ⅲ trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer（Prep-02/JSAP-05）. J Clin Oncol 49：190-194, 2019

3）Yanagimoto H, Satoi S, Yamamoto T, et al：Benefits of conversion surgery after multimodal treatment for unresectable pancreatic ductal adenocarcinoma. Cancers（Basel）12：1428, 2020

4）Satoi S, Yamaue H, Kato K, et al：Role of adjuvant surgery for patients with initially unresectable pancreatic cancer with a long-term favorable response to non-surgical anti-cancer treatments：results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 20：590-600, 2013

5）Ioka T, Kanai M, Kobayashi S, et al：Randomized phase Ⅲ study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer（KHBO1401- MITSUBA）. J Hepatobiliary Pancreat Sci 30：102-110, 2023

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

7）Le DT, Durham JN, Smith KN, et al：Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357：409-413, 2017

8）Doebele RC, Drilon A, Paz-Ares L, et al：Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours：integrated analysis of three phase 1-2 trials. Lancet Oncol 21：271-282, 2020

9）Drilon A, Laetsch TW, Kummar S, et al：Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378：731-739, 2018

10）Demetri GD, De Braud F, Drilon A, et al：Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive solid tumors. Clin Cancer Res 28：1302-1312, 2022

11）Imamura T, Ashida R, Ohshima K, et al：Genomic landscape of pancreatic cancer in the Japanese version of the Cancer Genome Atlas. Ann Gastroenterol Surg 7：491-502, 2023

Precis Oncol, 2018

13）Golan T, Hammel P, Reni M, et al：Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 381：317-327, 2019

14）Strickler JH, Satake H, George TJ, et al：Sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer. N Engl J Med 388：33-43, 2023

15）Ou SI, Jänne PA, Leal TA, et al：First-in-human phase Ⅰ/ⅠB dose-finding study of adagrasib（MRTX849）in patients with advanced KRAS（G12C）solid tumors（KRYSTAL-1）. J Clin Oncol 40：2530-2538, 2022

16）Yousef A, Yousef M, Chowdhury S, et al：Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma. NPJ Precis Oncol 8：27, 2024

17）Subbiah V, Kreitman RJ, Wainberg ZA, et al：Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers：the phase 2 ROAR trial. Nat Med 29：1103-1112, 2023

18）Bailey P, Chang DK, Nones K, et al：Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531：47-52, 2016

19）Cao L, Huang C, Cui Zhou D, et al：Proteogenomic characterization of pancreatic ductal adenocarcinoma. Cell 184：5031-5052, 2021

20）Hayashi H, Kohno T, Ueno H, et al：Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer. Pancreas 46：335-340, 2017

21）Yamai T, Ikezawa K, Sugimoto N, et al：Utility of Comprehensive Genomic Profiling Tests for Patients with Incurable Pancreatic Cancer in Clinical Practice. Cancers 15：970, 2023

22）Lowery MA, Ptashkin R, Jordan E, et al：Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas：Potential Targets for Intervention. Clin Cancer Res 24：4154-4161, 2018

23）Boerner T, Drill E, Pak LM, et al：Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma. Hepatology 74：1429-1444, 2021

24）Nakamura H, Arai Y, Totoki Y, et al：Genomic spectra of biliary tract cancer. Nat Genet 47：1003-1010, 2015

25）Abou-Alfa GK, Sahai V, Hollebecque A, et al：Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma：a multicentre, open-label, phase 2 study. Lancet Oncol 21：671-684, 2020

26）Javle M, Lowery M, Shroff RT, et al：Phase Ⅱ study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol 36：276-282, 2018

27）Goyal L, Meric-Bernstam F, Hollebecque A, et al：Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med 388：228-239, 2023

28）Zhu AX, Macarulla T, Javle MM, et al：Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation：the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol 7：1669-1677, 2021

29）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

30）Oh DY, Lee KH, Lee DW, et al：Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer：an open-label, single-centre, phase 2 study. Lancet Gastroenterol Hepatol 7：522-532, 2022

31）Chen J, Amoozgar Z, Liu X, et al：Reprogramming the intrahepatic cholangiocarcinoma immune microenvironment by chemotherapy and CTLA-4 blockade enhances anti-PD1 therapy. bioRxiv, 2023 Jan 27. doi：10.1101/2023.01.26.525680.

32）Brock A, Chang H, Huang S：Non-genetic heterogeneity--a mutation-independent driving force for the somatic evolution of tumours. Nat Rev Genet 10：336-342, 2009