Key result
Pixantrone shows insufficient single-agent activity in refractory HER2-negative metastatic breast cancer prompting early trial termination.
Why the study?
Anthracycline use in metastatic breast cancer is hindered by cardiotoxicity, whereas pixantrone is theorized to cause less cardiotoxicity.
Does pixantrone improve objective response rate in patients with refractory HER2-negative metastatic breast cancer?
RCT (n=45)
1:1
Yes
Does pixantrone improve objective response rate in patients with refractory HER2-negative metastatic breast cancer?
Pixantrone demonstrated insufficient anti-tumor activity in refractory HER2-negative metastatic breast cancer, although it appeared to have limited cardiotoxicity.
Does not support pixantrone monotherapy in refractory HER2-negative metastatic breast cancer; confirms insufficient activity despite limited cardiotoxicity.
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).
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Sideras et al. (2022) conducted an RCT in Metastatic Breast Cancer (n=45). Pixantrone vs. Pixantrone 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle was evaluated on Objective response rate (ORR). Pixantrone demonstrated insufficient single-agent activity in refractory HER2-negative metastatic breast cancer, yielding objective response rates of 8% and 5% in the two dosing cohorts, leading to early trial termination.
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