Dose-limiting effects of neutropenic events in six European audits of adjuvant breast cancer chemotherapy

Abstract

Listen

Translate article

619 Background: Retrospective audits of adjuvant breast cancer chemotherapy (CT) were performed in several European countries. Results of a combined analysis of six audits from Austria, Belgium, Germany, Spain and the UK are reported. Methods: Variables available in all six datasets were merged into a dataset of individual observations and their definitions were harmonised. We assessed the incidence of neutropenic events (NE) and of low average relative CT dose intensity (ARDI). Adjusted odds ratios (ORs) of low ARDI occurrence were calculated by robust multiple logistic regression. NE were defined as neutropenia-related hospitalisation, dose reduction ≥ 15%, and/or dose delay ≥ 7 days. Low ARDI was defined as ARDI ≤ 85%. Results: A total of 2633 patients had a mean age at diagnosis ± SD of 51.0 ± 11.3 years (inter-audit range (IAR): 48.0 ± 10.9 to 52.5 ± 11.7 years). Patients were post-menopausal in 51% of cases and 64% were hormone receptor positive. The diagnostic spread was stage I 19%, II 65%, III 16%. Fifty-eight percent received CMF-based regimens, 39% anthracycline-containing, and 3% other regimens. Concomitant radiotherapy was reported in 32%, and use of colony-stimulating factors (CSF) in 12%. In 3%, CSF use started in cycle 1. NE were observed in 20% of patients (IAR: 14–27%). Repeated NE were seen in 8% (IAR 6–11%). Low ARDI was observed in 14%. In those without and with NE low ARDI was observed in 9% vs 34% (p < 0.005). Low ARDI was independently associated with NE occurrence (OR 4.9, 95% CI 3.6–6.7); use of a non-anthracycline regimen (OR 1.5, CI 1.1–1.9); concomitant radiotherapy (OR 1.3, CI 1.1–1.5); and disease stage. ORs for stages II and III, compared to stage I, were 1.5 (CI 1.2–2.0) and 1.6 (CI 1.2–2.3). A more restrictive NE definition based on the cell count data available lead to an OR of 2.6 (CI 1.7–3.7) for low ARDI, with the other coefficients stable. Conclusions: NE occurred in a relevant proportion of patients receiving breast cancer CT and showed a robust association with low ARDI, which may affect treatment outcomes. Ongoing prospective research should address the development of risk models to target preventive measures and optimise CT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration INC-EU Study Group: Research Grant from Amgen EU