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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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

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docetaxel
Placebos
Breast Neoplasms
Adjuvant Chemotherapy
Asthenia
Febrile Neutropenia
Stomatitis
Mucositis
Fatigue
Diarrhea
Intercellular Signaling Peptides and Proteins
Therapeutics
axitinib
Hypertension
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. / Rugo, Hope S.; Stopeck, Alison T; Joy, Anil A.; Chan, Stephen; Verma, Shailendra; Lluch, Anna; Liau, Katherine F.; Kim, Sinil; Bycott, Paul; Rosbrook, Brad; Bair, Angel H.; Soulieres, Denis.

In: Journal of Clinical Oncology, Vol. 29, No. 18, 20.06.2011, p. 2459-2465.

Research output: Contribution to journalArticle

Rugo, Hope S. ; Stopeck, Alison T ; Joy, Anil A. ; Chan, Stephen ; Verma, Shailendra ; Lluch, Anna ; Liau, Katherine F. ; Kim, Sinil ; Bycott, Paul ; Rosbrook, Brad ; Bair, Angel H. ; Soulieres, Denis. / Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 18. pp. 2459-2465.
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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.",
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T1 - Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer

AU - Rugo, Hope S.

AU - Stopeck, Alison T

AU - Joy, Anil A.

AU - Chan, Stephen

AU - Verma, Shailendra

AU - Lluch, Anna

AU - Liau, Katherine F.

AU - Kim, Sinil

AU - Bycott, Paul

AU - Rosbrook, Brad

AU - Bair, Angel H.

AU - Soulieres, Denis

PY - 2011/6/20

Y1 - 2011/6/20

N2 - 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.

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