Effect of G-CSF primary prophylaxis on prevention of severe neutropenia in FOLFIRINOX therapy: A systematic review and a meta-analysis.

Abstract

e24086 Background: While FOLFIRINOX (leucovorin, fluorouracil, irinotecan and oxaliplatin) has been well established for gastrointestinal cancer treatment including pancreatic and colorectal cancer, high grade neutropenia and febrile neutropenia (FN) should be closely monitored due to the myelosuppressive nature of the regimen. The level of evidence remains to be examined for the effect of primary prophylaxis (PP) with granulocyte-colony stimulating factor (G-CSF) on prevention of such severe neutropenia in FOLFIRINOX therapy. Methods: PubMed and Cochrane database were searched for randomized controlled trials and observational studies that compared G-CSF PP to no PP (secondary prophylaxis and no prophylaxis combined) for neutropenia prevention in FOLFIRINOX regimen. Studies were included when the outcomes of neutropenia with higher than grade 3 or FN were reported. Heterogeneity was examined with I 2 statistics. A random-effects model was used for outcomes with high heterogeneity. Results: Out of 74 studies searched, we included 8 studies (1 RCT, 1 pooled analysis of RCTs and 6 observational studies) with 920 patients. 422 (45.9%) patients underwent G-CSF PP. The median ages ranged from 53.5 to 66. Male sex was 55.1%. Locally advanced or metastatic pancreatic cancer was the most common cancer type (n = 794, 86.3%), followed by colorectal cancer (n = 86, 9.3%), biliary tract cancer (n = 33, 3.6%), and gastric cancer (n = 7, 0.8%). ECOG performance status score was mostly 0-1 (79.6%) at baseline. Cases of grade 3 or higher neutropenia were significantly less common in patients who received G-CSF as PP upon the start of FOLFIRINOX therapy (Risk ratio (RR) 0.45 [95% confidence interval (CI) 0.32-0.64] (p < 0.00001)). FN also occurred to a significantly less extent in patients with G-CSF PP (RR 0.27 [95% CI 0.13-0.57] (p = 0.0005)). Hazard ratios (HRs) for overall survival (OS) were collected in 4 studies, of which 2 presented HR for OS comparing G-CSF PP group to no G-CSF group (HR 0.75 [95% CI 0.52 – 1.08] (p = 0.12) for Canton 2022; HR 0.46 [95% CI 0.30 - 0.73] (p = 0.001) for Carvalho de Brito 2023) and the other 2 presented HR for OS comparing G-CSF PP group to no PP group (HR 0.566 [95% CI 0.403-0.796] (p = 0.001) for Jung 2020; HR 0.35 [95% CI 0.16-0.76] (p = 0.005) for Moorcraft 2014). All 4 of them favored PP with G-CSF in terms of OS, but statistical significance could not be drawn together due to differences in HR measurement. Conclusions: These findings suggest that PP with G-CSF when starting a FOLFIRINOX regimen significantly reduces cases of severe neutropenia. Long-term efficacy of this preventive measure should be further studied.