Prophylaxis of chemotherapy-induced neutropenia with lipegfilgrastim in patients with lung cancer: final results from the non-interventional study NADIR

Abstract

Objective

Real-world evidence on the application of the granulocyte colony-stimulating factor lipegfilgrastim for the reduction of chemotherapy-induced neutropenia and febrile neutropenia (FN) is limited. The NADIR study aimed to evaluate effectiveness and safety of lipegfilgrastim as primary or secondary prophylaxis in patients with lung cancer undergoing chemotherapy in routine clinical practice.

Methods

The non-interventional study NADIR (German Clinical Trials Register (DRKS) Number DRKS00005711) enrolled 156 patients with small-cell lung cancer (SCLC) and 145 patients with non-small-cell lung cancer (NSCLC), who received lipegfilgrastim during chemotherapy. Primary endpoint was the incidence of severe neutropenia (CTCAE grade 3/4) and FN. The analysis was stratified for age groups (≤65 years vs. >65 years).

Results

Approximately half of the patients were aged >65 years (SCLC 54.5%; NSCLC 46.9%). Intention of antineoplastic treatment was mostly palliative (SCLC 89.1%; NSCLC 73.1%). Patients with high FN risk (SCLC 44.9%; NSCLC 28.3%) mostly received lipegfilgrastim for primary prophylaxis (SCLC 81.4%; NSCLC 70.7%). FN was reported in 1.9% SCLC and 1.4% NSCLC patients. At least one severe neutropenia was documented in 30.1% SCLC and 17.9% NSCLC patients. For NSCLC patients aged >65 years, less severe neutropenia was reported as compared to younger patients (14.7% vs. 20.8%). Lipegfilgrastim-related adverse events were reported in 10.3% SCLC and 7.7% NSCLC patients.

Conclusion

Lipegfilgrastim in routine clinical practice of patients with lung cancer showed similar effectiveness and safety as compared to the pivotal trial. Interestingly, in older patients severe neutropenia was reported less frequently. While most patients with high FN risk received lipegfilgrastim for primary prophylaxis as recommended, there are still 20–30% of patients at high FN risk without primary prophylaxis who could benefit from better adherence to guidelines.

Keywords:

• Lung cancer
• lipegfilgrastim
• neutropenia
• febrile neutropenia
• prophylaxis
• routine clinical practice

Transparency

Declaration of funding

This study was sponsored by TEVA GmbH.

Declaration of financial/other relationships

TF, CL, AL, HS, BN, MG, HE, RW, NF, JH, CDM, SG and KP have nothing to disclose. CG reports personal fees from GSK, from Pfizer, from AstraZeneca, from Roche, from Novartis, from BMS, from MSD, from TEVA, from Berlin Chemie, from Chiesi, from Boehringer Ingelheim and from Sanofi, outside the submitted work. AK reports documentation fees from iOMEDICO, during the conduct of the study; personal fees from Roche, from Amgen, from MSD, from BMS, from Sanofi, from Merck Serono, from Servier, from Aspen Germany, from MEDAC and from Bayer, outside the submitted work. JH is employee of TEVA GmbH. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

CG: Investigation, Resources, Writing – Review and Editing; TF: Conceptualization, Supervision, Writing – Review and Editing; CL: Investigation, Resources, Writing – Review and Editing; AL: Investigation, Resources, Writing – Review and Editing; HS: Investigation, Resources, Writing – Review and Editing; BN: Conceptualization, Methodology, Writing – Review and Editing; MG: Investigation, Resources, Writing – Review and Editing; HE: Investigation, Resources, Writing – Review and Editing; RW: Investigation, Resources, Writing – Review and Editing; AK: Investigation, Resources, Writing – Review and Editing; NF: Investigation, Resources, Writing – Review and Editing; JH: Conceptualization, Writing – Review and Editing; JH: Formal Analysis, Validation, Data Curation, Visualization, Writing – Review and Editing; CDM: Validation, Visualization, Writing – Original Draft; SG: Methodology, Validation, Writing – Original Draft, Project administration; KP: Methodology, Validation, Resources, Supervision, Writing – Original Draft. All authors gave their approval of the final version of the manuscript to be published.

Acknowledgements

The authors thank all patients, physicians and study teams participating in this study. We thank Melanie Frank (iOMEDICO) for support with the statistical analyses, Jochen Frank (iOMEDICO) for ongoing data quality control and Dr Mirja Grafetstätter (iOMEDICO) for preparation of the manuscript. Results of this study were presented in part at the Conference of the German Society of Hematology and Medical Oncology (DGHO), October 9–11, 2020.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics statement

This NIS was conducted and analyzed in accordance with Good Clinical Practice, and in compliance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from all individual participants included in the study.