October 2019: Toxicity analysis of neutropenic complications in adjuvant tailored dose-dense chemotherapy from the PANTHER study

The randomized phase III PANTHER trial evaluated efficacy and safety of adjuvant tailored dose-dense (tdd) epirubicin (E) and cyclophosphamide (C) followed by tdd docetaxel (D) compared to standard three-weekly epirubicin, cyclophosphamide and 5-fluorouracil (FEC) followed by docetaxel (D) in early breast cancer patients. An efficacy analysis of the primary endpoint demonstrated that the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer relapse-free survival (BCRFS; HR 0.79 [95%CI 0.61-1.01]; log-rank p=0.06; 5-year BCRFS, 88.7% vs 85.0%).

Myelosuppresion and subsequent neutropenia-related events such as febrile neutropenia or neutropenic infections are common side effects of chemotherapy. A granulocyte-colony stimulating factor (G-CSF) is often used to reduce the risk of neutropenic events. The aim of this exploratory toxicity analysis was to investigate neutropenic- and infection-related complications reported in the PANTHER study in relation to G-CSF use. A total of 98.9% of patients received primary G-CSF support during EC and 97.4% during D in the experimental group compared with 49.7% during FEC and 63.9% during D in the standard group. Overall, the use of G-CSF was associated with a lower risk for developing neutropenic events (OR 0.44, [95%CI 0.35-0.55]; p <0 .001). Chemotherapy delays due to neutropenia and leukopenia were significantly decreased among patients who received G-CSF (OR 0.098 [95%CI 0.06-0.15] and OR 0.32 [95%CI 0.18-0.58], respectively). Hence, primary prophylaxis with G-CSF reduces neutropenic events and is both feasible and effective, allowing also for dose-tailoring and increased dose intensity without excess myelotoxicity, which is essential for improved survival outcomes.

Papakonstantinou A, Hedayati E, Hellström M, Johansson H, Gnant M, Steger G, Greil R, Untch M, Moebus V, Loibl S, Foukakis T, Bergh J, Matikas A. Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncol. 2019; doi:10.1080/0284186X.2019.1670353.

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