Duration and de-escalation of FOLFIRINOX as first-line chemotherapy in advanced pancreatic adenocarcinoma.

e16370 Background: ModifiedFOLFIRINOX (FFX) is a standard first-line (1L) chemotherapy regimen for advanced pancreatic cancer. Toxicity is common during FFX, sometimes requiring treatment de-escalation, discontinuation, or switch to an alternative therapy. Optimal de-escalation and maintenance approaches during 1L FFX remain poorly defined. A better understanding of real-world treatment patterns and their clinical drivers can inform individualized therapeutic strategies during 1L FFX. Methods: We conducted an exploratory retrospective analysis of adult patients receiving 1L palliative-intent FFX at a single center (2015–2022). Data collected included demographic and clinical characteristics, baseline laboratory values, chemotherapy treatments, reasons for de-escalation and discontinuation of 1L chemotherapy, and overall survival. De-escalation was defined as omission of one or more agents (oxaliplatin, irinotecan, or fluoropyrimidine). Maintenance was defined as continuation of 1L therapy beyond cycle 8. Statistical analyses used t-tests and chi-square tests for continuous and categorical variables, respectively. Results: We identified 86 patients receiving 1L FFX for advanced pancreatic cancer. The median age was 63 years [IQR: 57-70], 63% were male, and 84% had metastatic disease. 14 patients (16%) discontinued 1L therapy after a single cycle of FFX. De-escalation of 1L FFX prior to reaching the maintenance phase occurred in 10 patients (12%). 31 patients (36%) continued 1L therapy into the maintenance phase. Baseline sodium was associated with continuing therapy into the maintenance phase (mean 138.1 vs 136.4 mmol/L, p < 0.05), but age, sex, albumin, bilirubin, transaminases, and creatinine were not (p > 0.05). FFX remained the most common regimen at cycle 9 (94%) followed by FOLFIRI (6%). However, 58% of patients who continued 1L treatment into the maintenance phase eventually had de-escalation of therapy, with oxaliplatin discontinuation due to neuropathy being the most common reason. The primary reasons for discontinuation of 1L therapy were cancer progression (72%) and treatment toxicity (14%). 57 patients (66%) received a second-line therapy, most commonly gemcitabine and nab-paclitaxel. Median survival among all patients was 7.2 months [IQR: 3.4-13.5], while those who reached the maintenance phase had a median survival of 14.6 months [IQR: 11.2-20.2]. Conclusions: Early discontinuation was more common than de-escalation during the first 8 cycles of 1L FFX. While many patients continued triplet chemotherapy beyond cycle 8, de-escalation of oxaliplatin was increasingly common during the maintenance phase. Future studies are needed to optimize tolerance and durability of 1L FFX in advanced pancreatic cancer.