Primary prophylaxis with pegylated-granulocyte colony-stimulating factor for patients with unresectable pancreatic cancer treated with modified-FOLFIRINOX: A randomized phase II trial

Abstract

Background: Pancreatic cancer patients treated with FOLFIRINOX often suffer from severe neutropenia leading to dose reductions and sometimes fatal outcomes. However, there is no high-level evidence for primary prophylaxis of peg-GCSF for those patients. We report the result of a multi-institutional, open-label, randomized phase II trial of the peg-GCSF for unresectable pancreatic cancer patients treated with first-line modified-FOLFIRINOX. Methods: Treatment-naïve patients with histologically confirmed locally advanced or metastatic pancreatic cancer from two Korean cancer centers were enrolled. Patients received oxaliplatin 85mg/m2 D1 + leucovorin 400mg/m2 D1 + irinotecan 150mg/m2 D1 + 5-FU 2,400mg/m2 46h continuous infusion, every other week. After 1:1 randomization, peg-GCSF (pegteograstim 6 mg, GC Biopharma Corp.) was administered on day 4 for initial 8 cycles for primary prophylaxis group, where no G-CSF was given for control group. Crossover to administer peg-GCSF was permitted if patients in control group developed grade 3-4 neutropenia during initial 8 cycles. Co-primary endpoints were grade 3-4 neutropenia or febrile neutropenia during initial 8 cycles of mFOLFIRINOX. Secondary endpoints included relative dose intensity (RDI), patient reported quality of life, bone pain, and survival. Results: Between Feb 2022 and Jan 2024, 38 patients were randomized to peg-GCSF primary prophylaxis group and 39 patients were randomized to control group. Peg-GCSF group patients had significantly less grade 3-4 neutropenia during initial 8 cycles of mFOLFIRINOX, compared to the control (1/38, 2.6% vs 15/39, 38.5%, P=0.0001). None of peg-GCSF group patients experienced febrile neutropenia, where 5 patients (12.8%) experienced febrile neutropenia in control group. Cumulative RDIs of mFOLFIRINOX until progression or 8th cycles were similar between two groups with 93%. Although this trial was not powered for survival comparison, median PFS (9.0 vs 7.3 months) was numerically longer for peg-GCSF group compared to control. OS was not reached for both arms, but hazard ratio was 0.48 for peg-GCSF group. Conclusions: Primary prophylaxis with peg-GCSF significantly reduced grade 3-4 neutropenia and febrile neutropenia in patients with locally advanced or metastatic pancreatic cancer treated with mFOLFIRINOX events. Considering the study design of permitting the crossover, cumulative RDI was similar. Further followup of survival and quality of life results will be presented. Clinical trial information: KCT0006536. Research Sponsor: GC Biopharma Corp. © (2024), (Lippincott Williams and Wilkins). All rights reserved.