{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T21:37:41Z","timestamp":1779399461309,"version":"3.53.1"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The clinical impact of\n                    <jats:italic>BRCA2<\/jats:italic>\n                    variants and tumor mutational burden (TMB) on first\u2010line regimen selection\u2014FOLFIRINOX (FFX) versus gemcitabine plus nab\u2010paclitaxel (GnP)\u2014for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Using the Center for Cancer Genomics and Advanced Therapeutics (C\u2010CAT) database, we analyzed patients with unresectable or recurrent PDAC treated with first\u2010line FFX or GnP. Overall survival (OS) and time to treatment failure (TTF) were compared, stratified by\n                    <jats:italic>BRCA2<\/jats:italic>\n                    pathogenic variants (PVs) and TMB status. A total of 4356 patients were included. In the overall population, GnP was associated with superior adjusted OS compared with FFX (adjusted hazard ratio [HR] 0.90,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.015), while TTF was comparable. In patients with\n                    <jats:italic>BRCA2<\/jats:italic>\n                    PVs (3.3%), FFX demonstrated a significantly higher objective response rate (66.7% vs. 33.3%) and longer TTF compared with GnP. However, OS in patients with\n                    <jats:italic>BRCA2<\/jats:italic>\n                    PVs was comparable between the two regimens (HR 1.11,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.665). Among patients with\n                    <jats:italic>BRCA2<\/jats:italic>\n                    PVs treated with GnP, OS was numerically longer with second\u2010line FFX than with nal\u2010IRI\/5\u2010FU\/leucovorin (HR 0.51;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.119). In patients without\n                    <jats:italic>BRCA2<\/jats:italic>\n                    PVs, OS was longer with GnP. TMB\u2010high status (2.9%) predicted significantly longer OS regardless of the first\u2010line regimen (HR 0.64,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In conclusion, GnP was associated with superior adjusted OS in the overall population. In\n                    <jats:italic>BRCA2<\/jats:italic>\n                    PV tumors, greater tumor shrinkage with first\u2010line FFX did not translate into longer OS, underscoring the importance of sequencing strategies that ensure timely exposure to platinum\u2010based therapy. TMB\u2010high tumors may benefit from timely access to immunotherapy.\n                  <\/jats:p>","DOI":"10.1111\/cas.70351","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:14:07Z","timestamp":1773011647000},"page":"1422-1433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>FOLFIRINOX<\/scp>\n                    vs. Gemcitabine\/Nab\u2010Paclitaxel for Pancreatic Cancer by\n                    <scp>\n                      <i>BRCA2<\/i>\n                    <\/scp>\n                    and\n                    <scp>TMB<\/scp>\n                    Status: A Japanese C\u2010\n                    <scp>CAT<\/scp>\n                    Database Study"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-8433","authenticated-orcid":false,"given":"Kazuyuki","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy Nagoya University Hospital  Nagoya Aichi Japan"},{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-7683","authenticated-orcid":false,"given":"Yuko","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy Nagoya University Hospital  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4700-6541","authenticated-orcid":false,"given":"Osamu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy Nagoya University Hospital  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy Nagoya University Hospital  Nagoya Aichi 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