臨床外科79巻2号

2024年02月発行

特集 ゲノム医学を外科診療に活かす！ 癌種別・ゲノム情報の治療選択への活用

胆道癌—胆道癌におけるprecision medicineの現状

著者： 石垣和祥¹²

所属機関： ¹東京大学医学部附属病院外来化学療法部 ²東京大学医学部附属病院腫瘍センター

ページ範囲：P.190 - P.196

【ポイント】
◆胆道癌はCGP検査で治療標的となる遺伝子異常が比較的多く検出される癌種の一つである．
◆FGFR2 fusionに関しては，保険で使用可能な薬剤が2種類（ペミガチニブ，フチバチニブ）あり，二次治療開始前に確実に拾い上げたい遺伝子異常である．
◆Tissue-basedのCGP検査が優先されるが，胆道癌ではCGP検査に適さない微小検体しかない場合も多く，その場合は多少感度が低下しても，liquid-basedのCGP検査を検討する．

参考文献

1）Sunami K, Naito Y, Aimono E, et al：The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan. Int J Clin Oncol 26：443-449, 2021

2）Okawa Y, Ebata N, Kim NKD, et al：Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase. Oncotarget 12：1540-1552, 2021

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

4）Nakamura Y, Taniguchi H, Ikeda M, et al：Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer：SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med 26：1859-1864, 2020

5）Berchuck JE, Facchinetti F, DiToro DF, et al：The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann Oncol 33：1269-1283, 2022

6）Oh D-Y, He AR, Qin S, et al：Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. N Engl J Med Evid 1：1-11, 2022

7）Akagi K, Oki E, Taniguchi H, et al：Real-world data on microsatellite instability status in various unresectable or metastatic solid tumors. Cancer Sci 112：1105-1113, 2021

8）Marabelle A, Fakih M, Lopez J, et al：Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab：prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 21：1353-1365, 2020

9）Maruki Y, Morizane C, Arai Y, et al：Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements：a prospective observational study（PRELUDE Study）. J Gastroenterol 56：250-260, 2021

10）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

-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med 388：228-239, 2023

12）Javle M, Roychowdhury S, Kelley RK, et al：Infigratinib（BGJ398）in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements：mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol 6：803-815, 2021

13）Hollebecque A, Borad M, Goyal L, et al：LBA12 Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients（pts）with an FGFR2-fusion or rearrangement（f/r）, FGFR inhibitor（FGFRi）-naïve cholangiocarcinoma（CCA）：ReFocus trial. Ann Oncol 33（Suppl 7）：S1381, 2022

14）Abou-Alfa GK, Macarulla T, Javle MM, et al：Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma（ClarIDHy）：a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 21：796-807, 2020

15）Javle M, Borad MJ, Azad NS, et al：Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer（MyPathway）：a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol 22：1290-300, 2021

16）Nakamura Y, Mizuno N, Sunakawa Y, et al：Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer（SGNTUC-019）：A Phase II Basket Study. J Clin Oncol 26：JCO2300606, 2023

17）Harding JJ, Fan J, Oh D-Y, et al；HERIZON-BTC-01 study group：Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer（HERIZON-BTC-01）：a multicentre, single-arm, phase 2b study. Lancet Oncol 24：772-782, 2023

18）Ohba A, Morizane C, Kawamoto Y, et al：Trastuzumab deruxtecan（T-DXd；DS-8201）in patients（pts）with HER2-expressing unresectable or recurrent biliary tract cancer（BTC）：An investigator-initiated multicenter phase 2 study（HERB trial）. J Clin Oncol 40（Suppl）：4006, 2022

19）Lee C-K, Chon HJ, Cheon J, et al：Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin：a multi-institutional phase 2 trial of the Korean Cancer Study Group（KCSG-HB19-14）. Lancet Gastroenterol Hepatol 8：56-65, 2023

20）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

21）Subbiah V, Wolf J, Konda B, et al：Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours（LIBRETTO-001）：a phase 1/2, open-label, basket trial. Lancet Oncol 23：1261-1273, 2022

22）Subbiah V, Cassier PA, Siena S, et al：Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med 28：1640-1645, 2022

23）Doebele RC, Drilon A, Paz-Ares L, et al；trial investigators：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

24）Hong DS, DuBois SG, Kummar S, et al：Larotrectinib in patients with TRK fusion-positive solid tumours：a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 21：531-540, 2020