P5-19-09: Phase II Trial of Ixabepilone Plus Carboplatin in Patients with Metastatic Breast Cancer: The ECLIPSE Study.
Authors: C Osborne, JD Challagalla, SR Fanning, CF Eisenbeis, FA Holmes, GG Monaghan, MA Neubauer, AC Rabe, V Raja, GJ Robbins, C Taboada, SJ Vukelja, ST Wilks, Y Wang, J-A Brown, L Asmar, J O'Shaughnessy
Journal: Cancer Research (2011)

Abstract Introduction: Ixabepilone adds to the antitumor effectiveness of capecitabine in both ER+ and triple negative (TN) breast cancer. Ixabepilone has antitumor activity in taxane-refractory patients, and novel combinations are needed in this poor prognosis population. Carboplatin combined with gemcitabine or paclitaxel has activity in metastatic breast cancer; there is also demonstrated activity of the gemcitabine/carboplatin combination in the ER+ versus TN subsets. A Phase I study of ixabepilone + carboplatin in solid tumor patients demonstrated the safety of this combination.1 We conducted a Phase II trial of ixabepilone + carboplatin at the doses and schedule used in the Phase I trial to determine its effectiveness in hormone receptor positive (HR+) and TN patients. Methods: This was a Phase II, open label, nonrandomized parallel, noncomparative study of 2 groups. Patients could have received up to 2 lines of treatment for metastatic disease. All patients received ixabepilone 20 mg/m2 on Days 1 and 8 and carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle. Patients were stratified as either (HR+) (n=50) or (TN) ER-/PR-/HER2− (n=53). Patients received drug until PD or intolerable toxicity. Patients continued treatment for as long as they responded (CR, PR, or SD). The primary objective was to evaluate objective response rate (ORR). Secondary objectives included evaluation of clinical benefit rate (CBR) defined as ORR (CR+PR)+SD≥6 months, progression-free survival (PFS), overall survival (OS), duration of responses, and toxicity. Results: Based on preliminary data, 96 patients (55 [57.3%] HR+ and 40 [41.7%] TN) received study treatment, with 1 patient found ineligible. Median age was 55.2 years; all were females; baseline PS of 0/1/2 was 50/44/2; stage at diagnosis I/II/III/IV/unknown was 12/38/23/21/2, respectively. PR was 26.3% overall. There were no CRs. CBR overall was 41.1% (39), 52.7% (29) for HR+ patients, and 25.6% (10) for TN patients. Median PFS was 7.6 months, and median OS was 12.7 months. The median time to response and duration of response in patients achieving a PR was 1.7 and 6.5 months, respectively. Grade 3/4 hematological toxicities included 49% neutropenia, 10.4% anemia, and 4.2% thrombocytopenia. The most common grade 3/4 non-hematologic toxicities included fatigue (8.3%), nausea (6.3%), neuropathy (6.3%), vomiting (5.2%), and dehydration (5.2%). Of 32 deaths during the study, one was due to neutropenic sepsis, and 25 were due to PD. Conclusion: The combination of ixabepilone plus carboplatin was a tolerable and active regimen for both HR+ and TN breast cancer. In general, it had expected hematologic and manageable non-hematological toxicities. Further follow-up of the remaining 12 patients still on treatment is ongoing. 1. Plummer R, et al. Clin Cancer Res. 2008 Dec 15;14(24):8288–8294. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-09.