FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study

Abstract

Background: Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer.

Materials and methods: This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity.

Results: Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0-22.3). The rates of grade 3-4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%).

Conclusion: 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France.

Implications for practice: FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.

Keywords: Advanced pancreatic cancer; FOLFIRINOX; Maintenance treatment; Quality of life; Real-life study.

Figure 1

Flow chart. Among the 150 patients who received FOLFIRINOX for advanced pancreatic cancer and a de‐escalation strategy, 147 patients were included. These patients received at least four cycles of FOLFIRINOX and received maintenance with FOLFIRI (n = 66), oral or intravenous 5FU (n = 52), FOLFOX (n = 25) or other type of maintenance (n = 4). Prognostic factors study was performed on patients who received maintenance with 5FU or FOLFIRI.Abbreviation: 5FU, 5‐fluorouracil.

Figure 2

Assessment of overall survival and first progression‐free survival (PFS1) under maintenance therapy. (A): Overall survival was 16.1 months (95% confidence interval [CI], 13.7–20.3). (B): Median PFS1 was 9.4 months (95% CI, 8.5–10.4).

Figure 3

Overall survival and first progression‐free survival (PFS1) curves in the FOLFIRI maintenance group (1), 5FU maintenance group (2), and FOLFOX maintenance group (3). (A): Overall survival. (B): Progression‐free survival. There is no statistically significant difference of overall survival or PFS1 between the FOLFIRI and 5FU arms. On the other hand, there seems to be a decrease of PFS1 and overall survival in the FOLFOX group.Abbreviation: 5FU, 5‐fluorouracil.

Figure 4

Analysis of first progression‐free survival (PFS1) under de‐escalation by FOLFIRI or 5FU depending on the response under FOLFIRINOX (n = 118). PFS1 was similar whether there was a response or stability under FOLFIRINOX, regardless of the chemotherapy regimen (5FU or FOLFIRI) (p = .5857).Abbreviation: 5FU, 5‐fluorouracil.

Figure 5

Analysis of second progression‐free survival (PFS2), which assesses survival on FOLFIRINOX reintroduced after progression under maintenance therapy by FOLFIRI (1) or 5FU (2). PFS2 was not available in the FOLFIRI group because of because of the low number of patients, and PFS2 was 2.8 months (95% confidence interval, 2.0–20.5) in the 5FU group.Abbreviations: 5FU, 5‐fluorouracil; NA, not available.