Comparative Efficacy and Toxicity of Modified FOLFIRINOX and Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Ductal Adenocarcinoma: A Real-World Retrospective Analysis.

Background Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited effective systemic therapies. Modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GN) are commonly used first-line regimens. The purpose of this study is to evaluate real-world efficacy (response rates, progression-free survival (PFS) and overall survival (OS)) and toxicity (grade 3/4 hematologic and non-hematologic toxicities) of first-line mFOLFIRINOX and gemcitabine plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma. Methods We conducted a retrospective analysis of 64 patients with advanced PDAC treated between May 2023 and May 2025. Thirty patients received GN, and 34 received mFOLFIRINOX. Efficacy outcomes included overall response rate (ORR), clinical benefit rate (CBR), PFS, and OS. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Statistical analyses included Kaplan-Meier survival estimates and Cox regression modeling. Results The median age was 59 years (range: 32-75), with a predominance of male patients (68.2%). Most had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 (89.1%). Patients receiving mFOLFIRINOX were younger and more likely to have tumors in the pancreatic head, whereas elevated CA19-9 levels were more common in the GN group. ORR was 57% in the GN arm and 52.9% with mFOLFIRINOX (P=0.179), while CBR was comparable (77% vs. 76.5%, P=0.985). The median progression-free survival of patients receiving GN was 6.97 months and 8.5 months with FOLFIRINOX (HR: 1.14; 95% CI: 0.58 - 2.22; P=0.713). mFOLFIRINOX had a median overall survival benefit (HR: 1.352; 95% CI 0.63 - 2.90; P=0.428), but this did not reach statistical significance. One-year OS was higher with mFOLFIRINOX (91.6% vs. 82.4%), as was 1.5-year OS (76.3% vs. 55.0%). Paradoxically, one-year PFS favored GN (32.5% vs. 20.3%). Grade 3/4 hematologic toxicities were more frequent with mFOLFIRINOX (e.g., neutropenia: 20% vs. 8.8%, anemia: 20% vs. 5.9%). GN was associated with more grade 3/4 vomiting (38.2% vs. 10%, P=0.009), diarrhea (26.5% vs. 3.3%, P=0.011), and neuropathy (29.4% vs. 6.7%, P=0.02). Dose modifications and treatment delays were similar, though delays were more frequent in the mFOLFIRINOX arm. Conclusions Both mFOLFIRINOX and GN demonstrated comparable efficacy in real-world treatment of advanced PDAC. mFOLFIRINOX offered better long-term OS but carried a higher risk of hematologic toxicity, while GN was associated with greater gastrointestinal and neurological adverse effects. Treatment selection should be guided by patient-specific factors such as comorbidities and tolerance to toxicity. Sequential treatment planning, including access to second-line therapy, significantly impacts survival and should be integral to care strategies.