Background: Chemotherapy-related adverse events (AEs) can negatively impact the treatment of pts. Managing and preventing these toxicities often require additional medications. This study examined the proportion of pts with mPDAC treated with 5-FU–based regimens in 2L who experienced AEs during treatment, and the proportion who received medication to manage those AEs. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment Jan 2016 to Aug 2020 from the Flatiron Health database. Pts included were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or liposomal irinotecan (nal-IRI). The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia and G3/G4 thrombocytopenia were determined using lab results and the grading criteria from the CTCAE v4.03. The occurrence of diarrhea and nausea/vomiting (N/V) were identified via ICD-10-CM codes. The use of atropine and granulocyte colony stimulating factor (G-CSF) during treatment was assessed. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs, medication use, and DOT were reported. Results: Of the 825 eligible pts, 29.0% (n=239) received FFX, 40.2% (n=332) received regimens containing nal-IRI, 24.0% (n=198) received FOLFOX, and 6.8% (n=56) received FOLFIRI. The median DOT (IQR) was 15.1 weeks (wks) (7.1 – 30.1), 12.9 wks (6.0 – 24.8), 11 wks (6.4 – 24.0), and 12.7 wks (8.3 – 24.6) for pts who received FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 thrombocytopenia (<50,000/mm³) presented in 9.6%, 2.4%, 8.1%, and 14.3% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (<1000/mm³) presented in 22.6%, 12.3%, 14.6%, and 19.6% of pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. The median (Q1-Q3) cumulative dose of the G-CSF pegfilgrastim was 18mg (12 – 45), 18mg (12 – 48), 24mg (12 – 36), and 30mg (13 – 48) for pts treated with FFX, nal-IRI, FOLFOX, and FOLFIRI, respectively. Atropine use was higher in pts treated with FFX and FOLFIRI (90.8% and 94.6%, respectively) than for pts treated with nal-IRI (75.6%). The full study results are reported in the table. Conclusions: In this study of AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of thrombocytopenia and neutropenia. Diarrhea was similar across the cohorts despite the high proportion of use in atropine for pts treated with FFX and FOLFIRI.