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

切除不能・再発膵癌に対する薬物療法

著者： 佐々木隆¹

所属機関： ¹がん研究会有明病院肝胆膵内科

ページ範囲：P.763 - P.767

【ポイント】
◆FOLFIRINOX療法とGEM＋nab-PTX併用療法の登場により，膵癌の治療成績は向上した．
◆膵癌の治療選択において，遺伝子検査の果たす役割がますます高まってきている．
◆RAS阻害薬の開発が進んできており，今後膵癌に対する臨床応用が期待されている．

参考文献

1）Burris HA 3rd, Moore MJ, Andersen J, et al：Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer：a randomized trial. J Clin Oncol 15：2403-2413, 1997

2）Conroy T, Desseigne F, Ychou M, et al：FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364：1817-1825, 2011

3）Von Hoff DD, Ervin T, Arena FP, et al：Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369：1691-1703, 2013

4）Ueno H, Ikeda M, Ueno M, et al：Phase Ⅰ/Ⅱ study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol 77：595-603, 2016

5）Ozaka M, Ishii H, Sato T, et al：A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol 81：1017-1023, 2018

6）Ohba A, Ueno H, Shiba S, et al：Safety and efficacy of S-IROX（S-1, irinotecan and oxaliplatin combination therapy）in patients with advanced pancreatic cancer：a multicenter phase 1b dose-escalation and dose-expansion clinical trial. Eur J Cancer 174：40-47, 2022

7）Ohba A, Ozaka M, Ogawa G, et al：Nab-paclitaxel plus gemcitabine versus modified FOLFIRINOX or S-IROX in metastatic or recurrent pancreatic cancer（JCOG1611, GENERATE）：a multicenter, randomized, open-label, three-arm, phase 2/3 trial. ESMO Congress 2023, Abstract 1616O, 2023

8）Wainberg ZA, Melisi D, Macarulla T, et al：NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma（NAPOLI 3）：a randomised, open-label, phase 3 trial. Lancet 402：1272-1281, 2023

9）Wattenberg MM, Asch D, Yu S, et al：Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer 122：333-339, 2020

10）Suker M, Beumer BR, Sadot E, et al：FOLFIRINOX for locally advanced pancreatic cancer：a systematic review and patient-level meta-analysis. Lancet Oncol 17：801-810, 2016

11）Matsumoto I, Kamei K, Omae K, et al：FOLFIRINOX for locally advanced pancreatic cancer：Results and prognostic factors of subset analysis from a nation-wide multicenter observational study in Japan. Pancreatology 19：296-301, 2019

12）Philip PA, Lacy J, Portales F, et al：Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer（LAPACT）：a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol 5：285-294, 2020

13）Williet N, Petrillo A, Roth G, et al：Gemcitabine/nab-paclitaxel versus FOLFIRINOX in locally advanced pancreatic cancer：a European multicenter study. Cancers（Basel）13：2797, 2021

14）Ozaka M, Nakachi K, Kobayashi S, et al：A randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer（JCOG1407）. Eur J Cancer 181：135-144, 2023

15）Wang-Gillamm A, Li CP, Bodoky G, et al：Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy（NAPOLI-1）：a global, randomized, open-label, phase 3 trial. Lancet 387：545-557, 2016

16）Mie T, Sasaki T, Okamoto T, et al：Treatment outcomes of nanoliposomal irinotecan as second-line chemotherapy after gemcitabine and nab-paclitaxel in metastatic and recurrent pancreatic cancer. Jpn J Clin Oncol 52：1399-1407, 2022

17）Mie T, Sasaki T, Takeda T, et al：Treatment outcomes and prognostic factors of gemcitabine plus nab-paclitaxel as second-line chemotherapy after modified FOLFIRINOX in unresectable pancreatic cancer. Cancers（Basel）15：358, 2023

-mutated metastatic pancreatic cancer. N Engl J Med 381：317-327, 2019

19）Pishvaian MJ, Blais EM, Brody JR, et al：Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling：a retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol 21：508-518, 2020

20）Marabelle A, Le DT, Ascierto PA, et al：Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer：results from the Phase II KEYNOTE-158 study. J Clin Oncol 38：1-10, 2020

21）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

22）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

23）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

mutations：results of the NCI-MATCH trial subprotocol H. J Clin Oncol 38：3895-3904, 2020

25）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

26）Nakayama I, Shinozaki E, Kawachi H, et al：Implementation of microsatellite instability testing for the assessment of solid tumors in clinical practice. Cancer Med 12：7932-7940, 2023

27）Quintanilha JCF, Storandt MH, Graf RP, et al：Tumor mutational burden in real-world patients with pancreatic cancer：genomic alterations and predictive value for immune checkpoint inhibitor effectiveness. JCO Precis Oncol 7：e2300092, 2023

28）Yoshino T, Pentheroudakis G, Mishima S, et al：JSCO-ESMO-ASCO-JSMO-TOS：international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol 31：861-872, 2020

29）Heestand GM, Kurzrock R：Molecular landscape of pancreatic cancer：implications for current clinical trials. Oncotarget 6：4553-4561, 2015

30）Hong DS, Fakih MG, Strickler JH, et al：KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 383：1207-1217, 2020

solid tumors（KRYSTAL-1）. J Clin Oncol 40：2530-2538, 2022

p.G12C-mutated advanced pancreatic cancer. N Engl J Med 388：33-43, 2023

mutation. J Clin Oncol 41：4097-4106, 2023

34）Hofmann MH, Gerlach D, Misale S, et al：Expanding the reach of precision oncology by drugging all KRAS mutants. Cancer Discov 12：924-937, 2022

35）Philip PA, Azar I, Xiu J, et al：Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma. Clin Cancer Res 28：2704-2714, 2022