A phase II study of ixabepilone plus trastuzumab for metastatic HER2-positive breast cancer.

Abstract

Abstract Abstract #3137 Background: The epitholones are a new class of antineoplastic agents which are microtubule inhibitors with low susceptibility to several mechanisms of drug resistance. Ixabepilone (BMS-247550, aza-epothilone B) has demonstrated efficacy as monotherapy or in combination with capecitabine (in anthracycline- and taxane-pretreated metastatic breast cancer) and has recently been approved for use in refractory breast cancer. A multicenter NCI-sponsored study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer.
 Methods: This phase II nonrandomized study enrolled two cohorts of patients. Cohort 1 received no prior chemotherapy or trastuzumab for metastatic disease and cohort two received one or two prior trastuzumab-containing regimens for metastatic disease. Patients in each cohort received the same treatment regimen of ixabepilone and trastuzumab. Patients received ixabepilone 40 mg/m2 as a 3-hour continuous infusion on day 1 of a 21-day cycle plus trastuzumab once every 21 days. For the initial treatment of trastuzumab, patients received 8 mg/kg IV, and for all subsequent trastuzumab treatments 6 mg/kg. Treatment was continued until disease progression or unacceptable toxicity. Endpoints included response rate (RR), time to progression (TTP), toxicity, and predictive biomarkers.
 Results: 39 women entered the study (median age 51, range 29-74) with 15 patients in cohort 1 and 24 patients in cohort 2. A median of 7 cycles of therapy were administered in each cohort. In cohort 1, there were 12 partial responses (PR), and 1 patient with stable disease for 5 months (SD). In cohort 2, there were 8 PRs and 9 patients with SD. Across both cohorts, the overall RR was 51%, with a clinical benefit rate (CR + PR + SD for at least 6 months) of 56%. Treatment-related toxicities included neuropathy (grade ≥2, 55%), myalgias (grade ≥2, 20%), anemia (grade ≥2, 18%), neutropenia (grade ≥2, 23%), and elevated transaminases (grade ≥2, 10%). There were no episodes of grade 2 or higher cardiac toxicity. Biomarker data will be presented.
 Conclusion: This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has an encouraging response rate as first- and subsequent- line therapy for metastatic breast cancer. Clinically significant neuropathy was the major toxicity, and appeared to be cumulative. Based on these results, further evaluation of ixabepilone plus trastuzumab is warranted. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3137.