By Charlene Laino
SAN ANTONIO, Tex -- December 15, 2008 -- For patients with metastatic breast cancer who have poor performance status and who show resistance to anthracyclines and taxanes, ixabepilone plus capecitabine improves overall survival, progression-free survival, and tumour response compared with capecitabine alone, according to results of 2 large phase 3 studies, presented at the 31st Annual San Antonio Breast Cancer Symposium (SABCS).
Symptomatic metastatic breast cancer patients with poor performance status pose a difficult therapeutic challenge, due to a worse prognosis and greater risk of toxicity from chemotherapy than patients with good performance status, stated PierFranco Conte, MD, University Hospital, Modena, Italy, speaking at a poster presentation here on December 14.
Dr. Conte and colleagues theorised that ixabepilone -- the first in a new class of antineoplastic agents -- plus capecitabine would offer a new option for such patients. The combination showed consistent clinical benefit compared with capecitabine alone in 2 large clinical trials of patients with metastatic breast cancer who had tumours resistant to anthracycline and a taxane (Thomas ES et al. J Clin Oncol. 2007;25:3399-3406) or pretreated with anthracycline and a taxane (Hortobagyi GN et al. 44th Annual Meeting of the American Society of Clinical Oncology [ASCO] 2008 Breast Cancer Symposium. Abstract 186).
The researchers sought to better evaluate treatment effect in the subset of patients with a Karnofsky performance status of 70 to 80 by performing a predefined pooled analysis of findings from both the Thomas and Hortobagyi studies.
Both studies had a similar design. A total of 1,973 patients with metastatic breast cancer who were previously treated with an anthracycline and a taxane were randomised to receive ixabepilone (40 mg/m2 IV over 3 hours, every 3 weeks) plus oral capecitabine (1,000 mg/m2 twice a day for 14 days, every 3 weeks) or oral capecitabine alone (1,250 mg/m2 twice a day for 14 days, every 3 weeks). A total of 606 (31%) patients in the 2 studies had a Karnofsky performance status of 70 to 80; of these, 314 received combination treatment and 292 received capecitabine alone.
Outcome data on progression-free survival, overall survival, and tumour response were available for 268 patients in the combination arm and 257 patients in the capecitabine monotherapy arm. The median progression-free survival time was 4.6 months in the combination arm compared with 3.1 months in the capecitabine monotherapy arm. This finding corresponded to a 24% reduction in progression-free survival in the capecitabine arm (P = .0021).
The median overall survival time was 12.3 months in the ixabepilone plus capecitabine arm versus 9.5 months in the capecitabine monotherapy arm. This finding corresponded to a 25% reduction in overall survival in the monotherapy arm (P = .0015).
The overall response rate was 36% in the combination arm versus 19% in the capecitabine monotherapy arm. Specifically, in the combination arm, 2% of patients had a complete response, 34% had a partial response, and another 40% had stable disease. In the capecitabine monotherapy arm, there were no complete responders, and 19% of patients showed a partial response; another 37% of patients had stable disease.
There was an increased incidence of adverse events, primarily neutropenia and peripheral neuropathy, associated with combination versus monotherapy, Dr. Conte said. Seventy-one percent of 310 patients in the combination arm for whom safety data were available developed grade 3/4 neutropenia compared with 11% of the 288 patients in the capecitabine monotherapy arm. Twenty-three percent of patients in the combination arm developed peripheral neuropathy compared with 1% in the monotherapy arm.
Dr. Conte noted that the adverse events were generally manageable by dose reduction or interruption.
"Ixabepilone plus capecitabine provides a new treatment option for symptomatic patients where the standard of care is single-agent sequential therapy," Dr. Conte concluded.
Funding for this study was provided by Bristol-Myers Squibb Company.
[Presentation title: Ixabepilone Plus Capecitabine Improves Overall Survival in Symptomatic Patients With Metastatic Breast Cancer Previously Treated With Anthracycline and Taxane in 2 Large Phase III Studies. Abstract 6114]
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