De-escalation and dose density in real-world patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.

Abstract

628 Background: FOLFIRINOX (FFX) is a recommended first-line (1L) treatment for patients (pts) with mPDAC and good performance status but is known for high toxicity. To make the regimen more tolerable for pts, clinicians may omit components and/or reduce doses (referred to as “de-escalation”). To better understand the frequency and degree of de-escalation in outpatient clinical practice, we examined real-world (RW) treatment patterns among mPDAC pts receiving FFX in 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2022 who initiated treatment with FFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. Receipt of FFX was defined as receiving all four regimen components within 28 days of 1L initiation. Modified FFX (mFFX) was defined as administration of <150mg/m2 of irinotecan or <2,720mg/m2 5-FU total (bolus + infusion) during cycle 1. 6-week dose density was defined as the actual dose received of each component in the 6 weeks following treatment initiation as a percent of the expected dose over 3 two-week cycles [expected FFX dose defined as 2800 mg/m2 of 5-FU (bolus + infusion), 400 mg/m2 of leucovorin, 180 mg/m2 of irinotecan, and 85 mg/m2 of oxaliplatin per cycle]. Results: 1,215 mPDAC pts met the study inclusion criteria, with >99% receiving mFFX. The median age at 1L initiation was 65yr (IQR: 58–71), 57% were male, 68% were white, 15% had an ECOG score of 0, 39% had an ECOG score of 1, and 6% had an ECOG of 2. The median number of FFX cycles was 5 (IQR: 2–9). In the first administration, 97% of pts received FFX/mFFX, 2% received FOLFIRI (omitting oxaliplatin), and 1% received other combinations. The number of pts in treatment declined over subsequent administrations, as did the number receiving FFX: by the 10th administration, 390 pts were treated, with 74% receiving mFFX, 13% FOLFIRI, 5% FOLFOX (omitting irinotecan), and 7% other combinations. At the 15th administration, 149 pts continued treatment, with 36% receiving mFFX, 44% FOLFIRI, 5% FOLFOX, 8% 5FU + leucovorin, and 7% other (either 5FU alone or with oxaliplatin and/or irinotecan). Median 6-week dose density was 69% for 5FU (IQR: 40–93%), 100% for leucovorin (IQR: 66–133%), 83% for irinotecan (IQR: 56–130%), and 99% for oxaliplatin (IQR: 68–127%). Conclusions: De-escalation was common among pts continuing FFX/mFFX treatment, with oxaliplatin the most frequently omitted component in later administrations. Over the 6 weeks following FFX treatment initiation, the actual vs. standard dose was lowest for 5FU, followed by irinotecan, while median leucovorin and oxaliplatin doses were close to standard dose over 3 two-week cycles. The omission of components of the regimen may indicate that mFFX lacks tolerability for many pts.