Real-world dose intensity (DI) and time to adverse events (AEs) in a commercial database during first-line (1L) treatment of metastatic pancreatic adenocarcinoma (mPDAC) with FOLFIRINOX (FFX), FFX without 5FU bolus, and gemcitabine + nab-paclitaxel (GnP).
Authors: Syvart Dennen, Marty Masek, Paul Cockrum, Ravi Kumar Paluri
Journal: Journal of Clinical Oncology (2025)

692 Background: Onset of severe AEs during 1L FFX and GnP treatment for mPDAC negatively impacts clinical outcomes, requiring supportive care and/or treatment adjustment. Occasionally they lead to discontinuation. The 5FU bolus may be omitted from FFX (FFXnb) to increase tolerability. We examined DI and time to key AEs (anemia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea/vomiting, and neuropathy) during 1L FFX, FFXnb, and GnP. Methods: This retrospective study utilized Optum Market Clarity claims + EHR linked data. Inclusion criteria were: adults diagnosed with mPDAC between 1/1/2015 and 5/31/2023; initiated 1L FFX, FFXnb, or GnP (index date) within -14 to +90 days; ≥6 pre- and ≥1 month post-index enrollment; ≥1 AE of interest in 1L. Follow-up was index to earliest of death, disenrollment, start of 2L, or last administration + 14 days. DI was defined as cumulative dose divided by follow-up in months. Grade 3/4 hematologic AEs (hAEs) were measured from lab values. Ungraded AEs were sourced from EHR notes and claims diagnoses. FFX was defined as including 5FU bolus + infusion in the 1st cycle; FFXnb as 5FU infusion only. Kaplan-Meier (KM) methods estimated time AE. Results: Median follow-up in months for patients (pts) with hAEs was: FFX 4.2; mFFX 3.6; GnP 3.1. Median DI (mg/m2/month) for FFX vs FFXnb pts with hAEs was: 5FU 4567 vs 4581; leucovorin 632 vs 398; oxaliplatin 119 vs 142; irinotecan 253 vs 251. For GnP, DI was: gemcitabine 2230; nab-paclitaxel 269. The table below presents sample size (N) and median (95% CI) time to AE. Median time to anemia was numerically 2–4 weeks shorter for GnP and FFXnb vs FFX. Time to neutropenia was 8–12 days less for FFXnb vs GnP and FFX. Time to thrombocytopenia was 7 weeks less for GnP vs FFX and FFXnb. Time to neuropathy was nearly 4 weeks shorter for FFXnb vs FFX and GnP. Conclusions: While neutropenia is higher risk for FFX vs GnP, prophylactic growth factor is standard during FFX, which may result in the similar onset time vs GnP. Early onset of severe thrombocytopenia differentiates the GnP sample. Oxaliplatin DI was higher for FFXnb vs FFX pts, and may be associated with earlier onset of anemia, neutropenia, diarrhea, and neuropathy. Research is merited on interactions between dosing, AE timing, and treatment discontinuation. Time to AE. Grade 3/4 hAEs FFX N FFXnb N GnP N FFX median days (95% CI) FFXnb median days(95% CI) GnP median days (95% CI) Anemia 47 25 97 64 (38–96) 36 (19–70) 47 (39–56) Neutropenia 75 53 112 35 (25–47) 23 (14–43) 31.5 (18–42) Thrombocytopenia 33 22 54 63 (35–79) 65.5 (32–94) 14 (13–34) Ungraded AEs Diarrhea 216 264 297 27.5 (22–36) 17.5 (14–27) 27 (21–36) Fatigue 211 267 418 34 (23–43) 27 (17–34) 27 (21–30) Nausea/vomiting 337 403 561 6 (3–8) 9 (7–14) 9 (7–12) Neuropathy 151 155 190 92 (70–112) 67 (48–79) 92 (80–111)