Non-Interventional Study Hexafil: G-CSF Use in Accordance to Guidelines?
Authors: Tesch Hans , Abenhardt Wolfgang , Dietze Lutz , Chang DeLi Tilly , Ottillinger Bertram 
Published: October 2019

Abstract
Abstract 2057

Purpose of the study:
Chemotherapy (CT) induced neutropenia (CIN) is a common complication in the treatment of cancer and often leads to modifications of antineoplastic treatment. Granulocyte-colony stimulating factors (G-CSF) are frequently used to prevent or treat CIN in cancer patients. The non-interventional observational study HEXAFIL on the use of biosimilar filgrastim (EP-2006) was conducted to provide further insight into its therapeutic efficacy and routine clinical use in Germany, especially in compliance with guidelines on the use of G-CSF (EORTC, ASCO).

Methods:
1460 patients who signed informed consents are to be enrolled at 100 German sites. Data is documented for up to 3 consecutive filgrastim-supported CT-cycles. Rates of modified CT-treatments (dose modification/discontinuation of drug) are calculated by the number and percentage of patients affected; data presented are based on the first CT-cycle. Inclusion/Exclusion criteria: www.germanctr.de.

Results:
By 7/2012, data of 955 patients were available. Patients' mean age was 59 years (19 to 89), 75% of them being female. Most common tumour entities were breast cancer (57.2%), NHL (10.7%), lung cancer (7.6%), ovarian cancer (4.0%) and Hodgkin lymphoma (3.1%). Substances most commonly used for chemotherapy were cyclophosphamide (50.7%), epirubicin (33.2%), docetaxel (23.6%), 5-fluorouracil (20.9%) and doxorubicin (15.6%). In line with published data only 1.9% of all patients experienced febrile neutropenia (FN), 8.7% neutropenic complications and 14% had leukopenia CTC 4 at nadir. As expected and according to guidelines the majority of patients received primary (39.3%, PP) or secondary prophylaxis (32.9%, SP) with biosimilar filgrastim, however, 25.8% were treated on demand (TX, i.e. after having experienced neutropenic complications in the first documented CT cycle or a drop in leukocytes putting the patient at acute risk of neutropenic complications). Interestingly, if viewed by the presence of baseline leukopenia, 76.9% of all patients without leukopenia (CTC 0) received G-CSF prophylaxis (PP/SP) but only 46.1% of all patients with leukopenia CTC 3/4. In patients without baseline leukopenia receiving filgrastim for PP, leukopenia CTC 3/4 at nadir was present in 32.9%, whereas in SP it was 50.6% and in TX 70.8%. Median filgrastim treatment duration was 4 d (1 to 14). Patients with PP received median 5 days of treatment starting on median day 6 after CT, whereas SP and TX patients were treated on median day 8 and 9, respectively, for a median duration of 3 days each. Accordingly, patients with neutropenic complications received treatment starting on median day 8 for 3 days (median), whereas patients without neutropenic complications started on median day 7 for 5 days (median); moreover, patients with FN only started biosimilar filgrastim therapy on median day 9. 93.9% of all documented patients received CT without any modification; in 4.6% of patients the dose of chemotherapy was modified and in 1.4% a chemotherapy drug was discontinued. Data indicate that patients with earlier and longer filgrastim treatment showed less chemotherapy disturbances, FN and neutropenic complications.

Conclusions:
Approximately 94% of all documented patients received filgrastim-supported CT-cycles without any modification of the CT-regimen. Yet, there is still room for improvement in prevention of CIN/FN in cancer patients as reflected by median start/treatment days and number of neutropenic complications. Moreover, daily injections should not impact the prophylactic use of G-CSF as revealed by self-assessment questionnaires in which patients reported handling of the needle guard system and of the pre-filled syringes to be easy or very easy (97.7% and 97.8%, respectively and calculated on questionnaires evaluable).

Disclosures:
Tesch: Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche: Honoraria; Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche; Sanofi Aventis: Consultancy. Abenhardt:Hexal: Honoraria. Dietze:Hexal: Honoraria. Chang:Hexal: Employment. Ottillinger:Hexal, Sandoz: Consultancy, Honoraria.