Over- and under-prophylaxis for chemotherapy-induced (febrile) neutropenia relative to evidence-based guidelines is associated with differences in outcomes: findings from the MONITOR-GCSF study

Abstract

PurposeIn the MONITOR-GCSF study of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim, 56.6% of patients were prophylacted according to amended EORTC guidelines, but 17.4% were prophylacted below and 26.0% above guideline recommendations.MethodsMONITOR-GCSF is a prospective, observational study of 1447 evaluable patients from 140 cancers centers in 12 European countries treated with myelosuppressive chemotherapy for up to 6 cycles receiving biosimilar GCSF prophylaxis. Patients were classified as under-, correctly-, or over-prophylacted with GCSF relative to guideline recommendations based on their chemotherapy risk, individual risk factors, and type of GCSF prophylaxis (primary versus secondary).ResultsDifferences between under- (17.4%), correctly- (56.6%), or over-prophylacted (26.0%) groups were found in terms of patient risk factors (age, performance status, history of FN, comorbid conditions) as well as prophylaxis patterns (type of prophylaxis, day of GCSF initiation, and GCSF duration). Rates of chemotherapy-induced neutropenia (CIN) (all grades), FN, and CIN-related hospitalizations were consistently lower in over-prophylacted patients relative to under- and correctly-prophylacted patients. No differences were observed between under- and correctly-prophylacted patients except for CIN/FN-related chemotherapy disturbances. No GCSF safety differences were found between groups (except for headaches).ConclusionsThe real-world evidence provided by the MONITOR-GCSF study indicates that providing GCSF support may yield better CIN, FN, and CIN/FN-related hospitalization outcomes if patients are prophylacted at levels above guideline recommendations. Patients who are under-prophylacted are at higher risk for disturbances to their chemotherapy regimens. Our findings support the guideline recommendation that CIN/FN risk be assessed at the beginning of each chemotherapy cycle.

Febrile neutropenia hospitalization due to pegfilgrastim on-body injector failure compared to single-injection pegfilgrastim and daily injections with reference and biosimilar filgrastim: US cost simulation for lung cancer and non-Hodgkin lymphoma

“…In addition, it may also be related to the MONITOR-GCSF finding that prophylaxis patterns deviated from what is recommended by the EORTC guidelines 9 . About a quarter of patients received prophylaxis that exceeded these guidelines 39 , and this over-prophylaxis was associated with a lower likelihood of FN episodes and FNrelated hospitalizations 38 .…”

Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A Combined Analysis of Phase III Studies

“…Although this step is necessary for all approved biologics, including reference products, concerns regarding the safety of biosimilars means that ongoing pharmacovigilance is particularly important to continue to monitor the long-term safety of biosimilars and build confidence in their use. Although EP2006 is well studied in the pharmacovigilance setting [23][24][25][26], this combined analysis of phase III confirmatory studies aimed to broaden the evidence base in breast cancer for the safety profile of biosimilar filgrastim and confirm that reports of TEAEs in the included studies are consistent with the known safety profile of filgrastim. As expected, TEAEs were reported in a similar incidence in the combined biosimilar group (98.7%), compared with the reference group (96.2%) ( Table 5).…”

Febrile neutropenia (FN) occurrence outside of clinical trials: occurrence and predictive factors in adult patients treated with chemotherapy and an expected moderate FN risk. Rationale and design of a real-world prospective, observational, multinational study

“…Patients were more likely to experience an FN episode if they had Eastern Cooperative Oncology Group status ≥2 anytime during the study or received antibiotic prophylaxis. Notably, patients who were ‘under-prophylacted’ with G-CSF were also more likely to experience FN [ 22 ]. Rates of FN were consistently lower in over-prophylacted patients compared to those under- and correctly-prophylacted.…”