PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer

作者：Jennifer J. Knox, Grainne M. O’Kane, Daniel A. King, Daniel A. Laheru, Amber N. Habowski, Kenneth H. Yu, Kimberly Perez, Andrew J. Aguirre, Zachary Coyne, Harry Harvey, Ronan Andrew McLaughlin, Raymond Jang, Robert C. Grant, Elena Elimova, Daniel J. Renouf, Sandra E. Fischer, Kai Duan, Stephanie Ramotar, Gun Ho Jang, Amy X. Zhang, Craig Devoe, Harshabad Singh, Michael J. Pishvaian, Fieke E. M. Froeling, Wasif M. Saif, Eileen M. O’Reilly, Erica S. Tsang, Brian M. Wolpin, Julie M. Wilson, Anna Dodd, Trevor J. Pugh, Xiang Y. Ye, Steven Gallinger, David A. Tuveson, Faiyaz Notta, Elizabeth M. Jaffee · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-00436 · 被引用次数：29 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Renal cell carcinoma treatment

PURPOSE To assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX [mFFX]) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers. PATIENTS AND METHODS Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2 . The primary end point was progression-free survival (PFS) between arms with 0.3 significance. The per-protocol (PP) population included patients who received one dose of chemotherapy. Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical). RESULTS Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months. The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio [HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat. Median overall survival (OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017). Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%. The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months ( P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months ( P = .36). The median...