CHICAGO—Heavily pretreated women with metastatic breast cancer had significant improvements in progression-free survival and overall response rate when treated with the combination of utidelone plus capecitabine compared with capecitabine alone, according to the results of a phase III trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 (abstract 1004).
In addition, “early analysis suggested that utidelone plus capecitabine improved overall survival in this heavily pretreated population, but further follow-up and evaluation is required,” the study presenter said. “Utidelone offers a new potential option for patients with metastatic breast cancer, especially for the treatment of anthracycline- and taxane-refractory metastatic breast cancer.”
Utidelone is a genetically engineered epothilone analog manufactured by fermentation. It is a microtubule stabilizer and an inhibitor of angiogenesis. Early phase studies of the drug in breast cancer produced an overall response rate of between 23% and 43%.
This phase III study enrolled 405 women with advanced breast cancer who had been previously treated with anthracycline and taxanes, and had four or fewer prior lines of therapy. The women were randomly assigned 2:1 to the therapeutic arm of utidelone plus capecitabine or the control arm of capecitabine alone. Patients who had stable disease or better could continue treatment for up to 12 cycles or until progression.
The primary endpoint was progression-free survival. According to the independent radiologic review committee, combination treatment with capecitabine plus utidelone produced significantly longer progression-free survival compared with capecitabine alone (median 8.28 months vs 4.73 months; P < .001). When evaluated by the investigators, the median progression-free survival for the combination arm was 6.90 months compared with 4.76 months (P = .001).
Patients assigned to combination therapy also had significantly improved overall response rate (38.1% vs 25.9%; P = .014) and clinical benefit rate (44.6% vs 32.8%; P = .025) compared with capecitabine alone.
Early data from the overall survival analysis suggested that utidelone plus capecitabine improves overall survival compared with capecitabine alone (median 16.1 months vs 11.6 months).
There was no significant difference in hematologic or gastrointestinal toxicities, or hepatic or liver function abnormalities between the two treatment arms. Only peripheral neuropathy occurred at a higher rate in the combination arm. The median time of improvement from grade 3 or above to grade 1 or better was 4 weeks.
The presenter pointed out the utidelone showed an advantageous and manageable safety profile in comparison to published observation data on ixabepilone, another epothilone analog that is currently approved in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to anthracycline and taxanes.