Abstract P4-16-04: Amrubicin as second- or third-line treatment for patients with HER2-negative metastatic breast cancer (MBC): Final results from a phase II trial of the Sarah Cannon Research Institute (SCRI)
Authors: Yardley DA , Barton J , Raefsky E , Harwin W , Priego V , Inclan A , Miletello G , Hart LL , Shastry M , Finney L , Hainsworth JD , Burris HA 
Published: August 2014

Abstract
Background: Anthracyclines are among the most effective agents in the treatment of breast cancer; however, dose-dependent cumulative cardiotoxicity limits their use. Amrubicin is a synthetic anthracycline topoisomerase II inhibitor demonstrating potent antitumor effects coupled with little potential for cardiotoxicity. We report the final results from a phase I/II trial of amrubicin as second- or third-line therapy for HER2-negative MBC.
Methods: Eligible patients (pts) included women with measurable HER2-negative MBC who had received 1 or 2 prior chemotherapy regimens for MBC. Previous anthracyclines were permitted if ≥ 6 months prior to study entry. Normal LVEF was required. Amrubicin 110 mg/m2 IV (dose established from phase I portion) was administered every 3 weeks until disease progression or intolerable toxicity; growth factor use was permitted. Disease evaluations were performed every 6 weeks and LVEF assessments every 12 weeks. Progression-free survival (PFS) was the primary endpoint; a median PFS ≥ 4.5 months would merit further evaluation of amrubicin in MBC. Toxicity, overall survival, and overall response rate (ORR) were secondary endpoints.
Results: Between 1/2010 and 3/2012, 78 pts were enrolled, and 66 pts are included in this analysis (ph I: 3 pts; ph II 63 pts). Baseline characteristics included: median age 59 years; hepatic metastases in 50%; ≥ 3 sites of metastatic disease in 32%. Triple-negative histology was noted in 27%; prior adjuvant chemotherapy in 50%; prior anthracyclines in 32%; and 2 prior cytotoxic regimens for MBC in 35%. Median treatment duration was 18 weeks (6 cycles), range 1- 24 cycles. The ORR was 21% in evaluable pts (2 CR, 10 PR); 5 of these 12 pts had prior anthracyclines. 14% were not evaluable. The clinical benefit rate (CBR) was 42% (CBR = CR+PR+SD≥ 4 months); 35% of these responders received ≥12 cycles of amrubicin. Median PFS for all pts was 4.0 months (95% CI 2.5- 5.8 months) and did not significantly differ by line of therapy administered (4.0 months as 2nd line vs 4.7 as 3rd line therapy). 36% of pts were free of progression at 6 months. Neutropenia was the most common grade 3/4 toxicity present in 42% and accompanied by fever in 7%. No grade 3/4 non-hematologic toxicity occurred in &gt; 5% pts. One pt previously treated with anthracyclines experienced a transient 20% LVEF decline to 44% at cycle 4. This recovered to baseline within 2 weeks and pt continued to receive 2 additional cycles of amrubicin before experiencing PD. No other grade 3/4 cardiac events were noted. In 3 pts, amrubicin was discontinued due to toxicity (G4 neutropenia, G2 thrombocytopenia, G2 nausea/vomiting/vertigo).
Conclusions: Amrubicin was active and well tolerated in the second- or third-line MBC setting with manageable toxicity. The ORR of 21% and median PFS of 4 months are comparable to other single agents in this setting. The observed CBR of 42%, and the fact that nearly 1/3 of these responders received ≥12 cycles of amrubicin with no cardiotoxicity, suggests that future evaluations of amrubicin in breast cancer are warranted.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-04.