Second-Line Systemic Therapy Following First-Line FOLFIRINOX or NALIRIFOX in Metastatic Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.
Pouyan Shaker, Daniyaal Kamran, Lingling Du, Shubham Pant, Jane E Rogers, Jonathan D Mizrahi
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引用次数: 0
Abstract
Purpose: FOLFIRINOX and NALIRIFOX are now preferred first-line treatments for metastatic pancreatic ductal adenocarcinoma (mPDAC), yet optimal second-line therapy after frontline triplet chemotherapy remains unclear. Prior evidence largely addressed second-line treatment after gemcitabine-based first-line therapy, limiting relevance today. We conducted the first contemporary systematic review and meta-analysis of second-line therapy after frontline triplet chemotherapy.
Methods: We searched MEDLINE, Embase, CINAHL, and PsycINFO through January 2026 for studies of second-line therapy after first-line FOLFIRINOX/NALIRIFOX in adults with advanced/metastatic PDAC. Two reviewers independently selected studies, extracted data, and assessed quality (ROBINS-I or RoB 2). Random-effects meta-analyses pooled median overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Registered in PROSPERO (CRD420251276176) per PRISMA 2020 guidelines.
Results: Twenty-three studies (3888 patients) met inclusion criteria, mostly retrospective cohorts after first-line FOLFIRINOX. Pooled median OS from second-line initiation was 7.57 months (95% CI, 6.00-9.55); pooled median PFS was 3.18 months (95% CI, 2.74-3.68). Pooled ORR was 11.6%; pooled DCR was 47.8%. Combination gemcitabine-based regimens outperformed monotherapy, particularly with ECOG 0-1. The only randomized phase-III trial (GEMPAX) showed significantly improved PFS and ORR with gemcitabine plus paclitaxel versus gemcitabine alone, without significant OS benefit. ECOG performance status was the strongest outcome predictor.
Conclusion: This first contemporary synthesis of post-triplet second-line therapy in mPDAC shows meaningful benefit in carefully selected, fit patients. Gemcitabine-based combination therapy is a reasonable option for ECOG 0-1 patients, though treatment should remain individualized based on performance status, toxicity, and preference. These findings provide contemporary benchmarks for practice and future trials.
期刊介绍：
The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.
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