Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis

Abstract

Introduction The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP. Methods This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models. Results The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS. Conclusions Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

Impact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer

“…63,64 Multiple studies have demonstrated that patients with metastatic PDAC treated with FOLFIRINOX and primary G-CSF prophylaxis experience reduced incidence of neutropenia but similar rates of febrile neutropenia compared with those treated with secondary G-CSF prophylaxis. [65][66][67] The impact of G-CSF administration on survival has been less clear, with one study identifying a benefit only for patients aged ,65 years, 65 and others finding a nonsignificant increase in OS between patients treated with primary or secondary G-CSF prophylaxis. 66,67 However, in the same studies, 38% to 60% of patients who did not receive primary G-CSF prophylaxis developed neutropenia requiring G-CSF treatment, complicating the effect of G-CSF on survival.…”

“…[65][66][67] The impact of G-CSF administration on survival has been less clear, with one study identifying a benefit only for patients aged ,65 years, 65 and others finding a nonsignificant increase in OS between patients treated with primary or secondary G-CSF prophylaxis. 66,67 However, in the same studies, 38% to 60% of patients who did not receive primary G-CSF prophylaxis developed neutropenia requiring G-CSF treatment, complicating the effect of G-CSF on survival. Nonetheless, the differences in survival outcomes of patients with metastatic disease treated with G-CSF and the patients in the present study could be explained by the diminished tolerance for chemotherapy in patients with advanced disease, for whom G-CSF enables continuation of treatment and dose intensity associated with survival.…”

Analyzing Flow Cytometry or Targeted Gene Expression Data Influences Clinical Discoveries—Profiling Blood Samples of Pancreatic Ductal Adenocarcinoma Patients

“…Nevertheless, studies on the effect of modified FFX-Lipeg show an increase in granulocytes, caused by lipegfilgrastim. The addition of lipegfilgrastim has been shown to decrease the incidence of neutropenic events and prolong the progression-free survival of patients [43,44].…”