Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

Kostandinos Sideras, David W Hillman, Karthik Giridhar, Brenda F Ginos, Richard C Tenglin, Heshan Liu, Beiyun Chen, Winston Tan, Gerald G Gross, Rex B Mowat, Amylou C Dueck, Edith A Perez, Alvaro Moreno-Aspitia, Kostandinos Sideras, David W Hillman, Karthik Giridhar, Brenda F Ginos, Richard C Tenglin, Heshan Liu, Beiyun Chen, Winston Tan, Gerald G Gross, Rex B Mowat, Amylou C Dueck, Edith A Perez, Alvaro Moreno-Aspitia

Abstract

Background: Anthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.

Methods: Intravenous pixantrone was administered at 180 mg/m2 every 3 weeks (group A) versus 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.

Results: Forty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).

Conclusion: Pixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: NCT01086605).

Keywords: anthracycline; breast cancer; cardiotoxicity; pixantrone; randomized phase II.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Kaplan-Meier plots for progression-free and overall survival by dosing schedule. Group A received pixantrone at 180 mg/m2 every 3 weeks and group B received pixantrone 85 mg/m2 on days 1, 8, and 15 of 4-week cycles.
Figure 2.
Figure 2.
Change in ejection fraction at the end of treatment as compared to baseline.
Figure 3.
Figure 3.
(A) Kaplan-Meier plots for progression-free survival (PFS) and overall survival by CTC cut-off (negative <5 CTCs, positive ≥5 CTCs). (B) Kaplan-Meier plots for overall survival (OS) and overall survival by CTC cut-off (negative <5 CTCs, positive ≥5 CTCs).

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Source: PubMed

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