Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer

Hope S. Rugo, Alison T. Stopeck, Anil A. Joy, Stephen Chan, Shailendra Verma, Anna Lluch, Katherine F. Liau, Sinil Kim, Paul Bycott, Brad Rosbrook, Angel H. Bair, Denis Soulieres

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86 Scopus citations

Abstract

Purpose: This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC). Patients and Methods: Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP). Results: In all, 168 patients were enrolled; 112 were randomly assigned to axitinib and 56 to placebo. Median TTP was numerically longer in the combination arm than in the placebo arm (8.1 v 7.1 months), but this difference was not statistically significant (hazard ratio, 1.24; 95% CI, 0.82 to 1.87; one-sided P = .156). The difference in median TTP was greatest among patients who had received prior adjuvant chemotherapy (9.2 v 7.0 months; P = .043, prespecified subgroup analysis). Objective response rate was higher in the combination arm (41.1% v 23.6%; P = .011). The most common grades 3 to 4 treatment-related adverse events (combination/placebo) included diarrhea (10.8%/0%), fatigue (10.8%/5.4%), stomatitis (12.6%/1.8%), mucositis (9.0%/0%), asthenia (7.2%/0%), and hypertension (4.5%/0%). Three patients in the combination arm experienced serious thromboembolic events (one death). Febrile neutropenia was more frequent in the combination arm (15.3% v 7.1%); rates of other hematologic toxicities were comparable. Increased toxicity with axitinib was generally managed by dose reduction and/or growth factor support. Conclusion: The addition of axitinib to docetaxel did not improve TTP in first-line MBC treatment. Combination therapy may be more effective in patients previously exposed to adjuvant chemotherapy.

Original languageEnglish (US)
Pages (from-to)2459-2465
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number18
DOIs
StatePublished - Jun 20 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Rugo, H. S., Stopeck, A. T., Joy, A. A., Chan, S., Verma, S., Lluch, A., Liau, K. F., Kim, S., Bycott, P., Rosbrook, B., Bair, A. H., & Soulieres, D. (2011). Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. Journal of Clinical Oncology, 29(18), 2459-2465. https://doi.org/10.1200/JCO.2010.31.2975