Providing prophylactic treatment with granulocyte-colony stimulating factor to patients receiving chemotherapy may yield better chemotherapy-induced neutropenia, febrile neutropenia, and related hospitalization outcomes if patients receive prophylaxis at levels above guideline recommendations, according to a recent study.
Providing prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) to patients receiving chemotherapy may yield better chemotherapy-induced neutropenia (CIN), febrile neutropenia (FN), and CIN/FN-related hospitalization outcomes if patients receive prophylaxis at levels above guideline recommendations, according to a recent study published online in Support Care Cancer.
Carsten Bokemeyer, MD, PhD, and colleagues also concluded that patients who are under-prophylacted are at higher risk for disturbances to their chemotherapy regimens. The study’s conclusions are based on data from the MONITOR-GCSF study, a prospective, real-world, observational study of patients with cancer receiving myelosuppressive chemotherapy with biosimilar filgrastim (Zarxio), referenced on Neupogen, per best clinical judgment for adults with stage 3 or 4 breast, ovarian, bladder, or lung cancer; metastatic prostate cancer; and stage 3 or 4 diffuse large B-cell lymphoma, or multiple myeloma. Patients were followed for a maximum of 6 chemotherapy cycles. Hexal and Sandoz, sponsors of the biosimilar product, supported the study.
Evidence-based guidelines for prophylactic treatment for CIN and FN from the European Organization for Research and Treatment of Cancer (EORTC) and the National Comprehensive Cancer Network recommend that clinical decision-making be based on the relative myelotoxicity of patients’ chemotherapy regimens and the presence of potential risk factors. Prophylaxis with G-CSF is indicated for patients treated with chemotherapy with a 20% or more FN risk and for patients receiving chemotherapy with an FN risk of 10% to 20% if they also present with risk factors. Prophylactic treatment is not recommended for patients who have an FN risk of less than 10% following chemotherapy.
By the time that the biosimilar filgrastim was approved by the European Medicines Agency (2008) and the MONITOR-GCSF study launched (2010), 2 decades of evidence with reference filgrastim had already accumulated. Much of that evidence was summarized in the original updated EORTC guidelines, reviews, and meta-analyses. However, it became apparent that “the normative, trial-based prophylaxis pattern of treating with standard [G-CSFs] through the nadir of the absolute neutrophil count was being replaced with shorter regimens varying across tumor types in the average number of injections,” the report’s authors said. These deviations from guidelines in daily clinical practice suggest “either questionable clinical practice” or the opportunity to provide new real-world data to integrate into guidelines as evidence moves from initial clinical trial-based findings to incorporation of real-world data from mature clinical experience.
In the multicenter, longitudinal MONITOR-GCSF study of practice patterns and outcomes associated with CIN and FN prophylaxis with biosimilar filgrastim, the authors reported that 56.6% of 1444 patients received prophylaxis according to amended EORTC guidelines, but 17.4% were prophylacted below and 26.9% above guideline recommendations. The researchers wanted to further explore the impact of prophylaxis intensity below or above guideline-recommended levels, and performed analyses stratified by prophylaxis intensity (under, correctly, or over-prophylacted) that compared patients in terms of demographics, clinical status at the start of chemotherapy, filgrastim prophylaxis patterns, and clinical and safety outcomes.
The 3 cohorts in the current study consistently differed overall in the observed rates of CIN grades 1 to 4; CIN grades 3 or 4; CIN grade 4; and FN, CIN/FN-related hospitalizations, and composite outcome score (all P≤.001). The proportions of patients experiencing CIN/FN-related chemotherapy disturbances were not statistically different across cohorts; however, the proportion of cycles with chemotherapy disturbances was highest among under-prophylacted patients (P = .032). Relative to over-prophylacted patients, under-prophylacted patients were at significantly higher risk for adverse outcomes over the period of chemotherapy, including a 2-fold increased risk of disruptions to their chemotherapy regimens and a 3-fold greater likelihood of CIN/FN-related hospitalizations.
The researchers write that based on their results, providing G-CSF support may yield better CIN, FN, and CIN/FN-related hospitalization outcomes if patients are prophylacted at levels above guideline recommendations. Their findings do not mean that over-prophylaxis is indicated for all patients; however, the results may merit consideration of over-prophylaxis for selected patients, as those who received inadequate G-CSF prophylaxis are at markedly higher risk for poor outcomes.