Phase 2 results of ABT-751 in subjects with taxane-refractory breast cancer: Interim analysis
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Background: Therapy is limited for subjects with taxane-refractory metastatic breast cancer. ABT-751, an oral antimitotic agent that binds to the colchicine site of β-tubulin and prevents microtubule polymerization, has shown antitumor activity in breast xenograft models. In addition, ABT-751 is not an MDR substrate, making it an attractive drug candidate for taxane-refractory patients.
Methods: This Phase 2, open label, multi-center study evaluated the safety and efficacy of ABT-751 in subjects with advanced breast cancer (N = 18). For each cycle, subjects received 200 mg ABT-751 orally once daily for 21 consecutive days followed by a 7-day break. Safety was evaluated by adverse events (AEs) and laboratory assessments, while tumor response was assessed radiographically every 2 cycles using RECIST. Time to progression (TTP) was analyzed using Kaplan-Meier methodology.
Results: The median duration of therapy was 2 cycles (range 1 to 8). AEs were reported for 17/18 subjects, and 9/18 (50%) subjects experienced serious adverse events (SAEs). The most commonly reported AEs, regardless of causality, were constipation (78%), asthenia (56%), nausea (44%), and abdominal pain (33%). The most common Grade 3 or 4 AEs possibly or probably related to study drug were asthenia (11%), constipation (11%), and ileus (11%). The most common SAE was ileus (17%). Three subjects (17%) experienced SAEs considered possibly related to study drug, the most common of which were ileus (11%) and dehydration (6%). The median TTP was 1.8 months (95% CI = 1.4 - 2.3). There were no partial or complete responses, although two subjects exhibited stable disease for 7 to 8 cycles. All 18 subjects have discontinued the study. This study was designed to target a 25% response rate in an advanced taxane-refractory patient population. The target response rate was not met based on the results of this interim analysis.
Conclusions: Although the 21-day dosing regimen for ABT-751 was feasible, these data do not suggest a compelling tumor response with single-agent ABT-751 therapy in this highly advanced, taxane-refractory patient population. Future studies may explore potential synergism between ABT-751 and other cytotoxic agents.
Publication (Name of Journal)
Journal of Clinical Oncology
DOI
https://doi.org/10.1200/jco.2005.23.16_suppl.724
Recommended Citation
Washington, D.,
Storniolo, A.,
Saleh, M.,
Tan-Chiu, E.,
Hagey, A.,
Medina, D.,
Meek, K.,
Cernohous, P.,
Gordon, G.
(2005). Phase 2 results of ABT-751 in subjects with taxane-refractory breast cancer: Interim analysis. Journal of Clinical Oncology, 23(16).
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/9
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.