Real-world overall survival and time to next treatment in patients with metastatic pancreatic ductal adenocarcinoma who received FOLFIRINOX and modified FOLFIRINOX in the first line.

Abstract

629 Background: FOLFIRINOX (FFX) is a recommended first line (1L) treatment option for patients (pts) with mPDAC but is known for its high toxicity. Efforts to balance pts’ quality of life (QoL) during treatment with treatment effectiveness have led to the use of modified FOLFIRNOX (mFFX) regimens that employ decreased doses of FFX components. Further evidence is needed to assess OS and progression-free survival (PFS) among pts who receive FFX or mFFX treatment in the real world compared to the trial setting. We identified a real-world (RW) sample of pts with mPDAC treated with FFX and mFFX in 1L and assessed their OS, and, as a RW proxy for PFS, TTNT. Methods: This retrospective observational study utilized the Flatiron Metastatic Pancreatic Cancer Enhanced Data Mart. Adult pts diagnosed with mPDAC between January 2014 and May 2022 who initiated treatment with FFX or mFFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. mFFX was defined as administration of <150mg/m2 of irinotecan or <2,720mg/m2 5-FU total (bolus+infusion) during cycle 1; doses greater than these were considered FFX. TTNT was defined as duration between 1L treatment initiation and the start of second line therapy or death. Kaplan-Meier analyses were used to assess median OS and TTNT from the start of 1L FFX or mFFX treatment and log-rank tests for the statistical significance of differences in OS and TTNT. Results: 2,212 mPDAC pts met the study inclusion criteria, with 507 pts (23%) receiving FFX and 1,705 pts (77%) receiving mFFX in 1L. For FFX vs. mFFX, the median age at 1L initiation was 63yr vs. 65yr, 72% vs. 56% were male, 67% vs. 63% were white, 36% vs. 30% had an ECOG score of 0, 31% vs. 32% had an ECOG score of 1, and 83% vs. 81% received treatment at community oncology centers. For FFX vs. mFFX, median OS was 9.5 (95% CI: 8.9–10.7) vs. 9.0 months (95% CI: 8.4–9.7) (p=.452) and median TTNT was 4.8 (95% CI: 4.5–5.5) vs. 4.8 months (95% CI: 4.5–5.2) (p=.256). Conclusions: In a RW sample of 2,212 pts receiving 1L FFX and mFFX at primarily community oncology practices in the United States from 2014–2022, more than three-quarters received mFFX. Pts experienced similar median OS and TTNT across the two regimens, indicating that full-strength FFX may provide little benefit to OS in exchange for its increased toxicity. In the PRODIGE 4/ACCORD 11 trial of unmodified FFX, conducted earlier (2005–2009) among a group of 342 French pts, median OS was 11.1 months (95% CI: 9.0–13.1) and median PFS was 6.4 months (95% CI: 5.5–7.2). The median RW OS of FFX and mFFX pts in our study was numerically lower than the trial, as was RW TTNT compared with trial PFS. Future research should seek to understand the factors driving differences in RW and clinical trial outcomes as well as to assess the tradeoff between regimen toxicity and survival benefit.