NeoPancONE: GATA6 expression as a predictor of benefit to peri-operative modified FOLFIRINOX in resectable pancreatic adenocarcinoma (r-PDAC): A multicentre phase II study.

作者：Ronan Andrew McLaughlin, Derek J. Jonker, Paul J. Karanicolas, Yoo‐Joung Ko, Stephen Welch, Daniel J. Renouf, Kimberly A. Bertens, Carol-Anne Moulton, Michael J. Raphael, Shiva Jayaraman, Xiang Y. Ye, Amy Zhang, Tae Kyoung Kim, Korosh Khalili, Kai Duan, Sandra E. Fischer, Grainne M. O’Kane, Anna Dodd, Steven Gallinger, Jennifer J. Knox · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4011 · 被引用次数：7 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Lung Cancer Diagnosis and Treatment

4011 Background: Modified FOLFIRINOX (mFFX) is increasingly used in the perioperative setting in r-PDAC and patients (pts) would benefit from a biomarker approach. GATA6 expression enriches for the classical RNA subtype, associated with improved OS in advanced PDAC. Low expression identifies the basal subtype which may predict mFFX resistance. NeoPancONE is a single arm Phase II multicentre study evaluating clinical outcomes and investigating GATA6 as a biomarker of response to perioperative mFFX in r-PDAC. Methods: Pts were enrolled following central radiology review (CRR) and underwent an EUS FNB for GATA6 in-situ hybridization (ISH). Six cycles of mFFX were planned pre and postoperatively. The primary endpoint was 1 yr event-free survival (EFS) according to GATA6 ISH (high vs low). Secondary endpoints include OS, RECIST response, SAEs, R0 resection rates and RNA subtyping by PurIST. Statistical assumptions used a ratio of 3:1 GATA6 high:low, with a 1 yr EFS of 65% for high and 34% for low (HR 2.5, 80% power, 2 sided alpha 0.05). KM method and log-rank test were used. Results: Between Sep-2020– Sep 2023, 146 pts were screened and 84 enrolled (58%) at 8 Canadian centres. CRR deemed 39 (27%) ineligible. Clinical data are summarized (Table). GATA6 ISH was analysed in 74 (88%); 62 (84%) were high, 16% low. At a median follow up of 24.5 mos, the med EFS and OS in the ITT were 16.1 mos (95 CI; 13-21) and 34.2 mos (95 CI; 28-NE). Med OS in the 73 pts who underwent surgery was 35.6...