### Neoadjuvant / Perioperative - [[PREOPANC-1]] (2020): Neoadjuvant *gemcitabine-based chemoradiotherapy* improved R0 resection, local control, and DFS, with later OS benefit—particularly in BR-PDAC. - [[SWOG S1505]] (2020): Perioperative **mFOLFIRINOX** and **gemcitabine/nab-paclitaxel** demonstrated feasibility in resectable PDAC. - [[PANACHE01-PRODIGE48]] (2022): Explored perioperative **FOLFIRINOX** based strategies in resectable PDAC. - [[ALLIANCE A021501]] (2022): Neoadjuvant **mFOLFIRINOX** produced favorable outcomes in BR-PDAC, while routine addition of **hypofractionated RT** did not improve results. - [[NEONAX]] (2023): Evaluated perioperative **gemcitabine/nab-paclitaxel** strategies in resectable PDAC. - [[NORPACT-1]] (2024): Perioperative **FOLFIRINOX** failed to improve OS versus upfront surgery in resectable PDAC despite improved pathologic outcomes. - [[PREOPANC-2]] (2025): **Total neoadjuvant FOLFIRINOX** did not demonstrate clear OS superiority over gemcitabine-based chemoradiotherapy. --- ### Adjuvant Trials - [[GITSG]] (1985): Survival benefit from adjuvant **5-FU chemoradiation** versus observation after PDAC resection. - [[CONKO-001]] (2007): Established adjuvant **gemcitabine** as standard of care after PDAC resection through significant DFS and long-term OS benefit. - [[ESPAC-4]] (2017): Adjuvant **gemcitabine + capecitabine** improved OS versus **gemcitabine** alone following PDAC resection. - [[PRODIGE-24]] (2018): Adjuvant **mFOLFIRINOX** dramatically improved DFS and OS versus **gemcitabine**, establishing modern adjuvant standard therapy for fit patients. - [[APACT]] (2019): Adjuvant **gemcitabine + nab-paclitaxel** failed to significantly improve independently assessed DFS despite favorable investigator-assessed outcomes. --- ### Metastatic - [[EXTEND]] (2024): In carefully selected oligometastatic PDAC, adding comprehensive **metastasis-directed therapy** (local treatment to all visible disease sites, usually **SBRT/ablative radiation**) to systemic therapy improved PFS versus systemic therapy alone, supporting the concept of an actionable oligometastatic disease state. - [[RASolute 302]] (2026): Oral **daraxonrasib** significantly improved OS, PFS, response rate, and patient-reported outcomes versus **investigator’s-choice chemotherapy** in previously treated metastatic PDAC, supporting active RAS inhibition as a major therapeutic advance. --- ### Locally Advanced / Unresectable Disease - [[LAP07]]: Evaluated consolidative chemoradiation strategies in locally advanced PDAC after induction chemotherapy. - [[CONKO-007]]:Compared continued chemotherapy versus chemoradiation following induction therapy in locally advanced PDAC. - [[NEOLAP-AIO-PAK-0113]] --- ### Precision / Targeted / Biomarker-Directed - [[POLO]]: Maintenance olaparib improved progression-free survival in germline BRCA-mutated metastatic PDAC. - [[KRYSTAL-1]]: Evaluated KRAS G12C inhibition in advanced solid tumors including PDAC. - [[CodeBreaK]]: Demonstrated activity of KRAS G12C inhibition across advanced solid tumors including pancreatic cancer. --- ### Immunotherapy / Emerging Therapies [[KEYNOTE-158]]: Established pembrolizumab activity in MSI-high/dMMR solid tumors including rare PDAC subsets.