CHICAGO — The genetically engineered epothilone analog, utidelone, in combination with capecitabine significantly improved progression-free survival and objective response rates in patients with metastatic breast cancer who were heavily pretreated, compared with capecitabine alone, results of a phase 3 trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting have shown.1
“Utidelone officers a new potential option for patients with metastatic breast cancer, especially for the treatment of anthracycline- and taxane-refractory disease,” said Xi-Chun Hu, MD, PhD, of Fudan University Shanghai Cancer Center, Shanghai, China.
The microtubule stabilizing agent plus capecitabine demonstrated an “advantageous and manageable safety profile, in contrast to published observation with ixabepilone,” he said. This included very mild myelosuppression, very limited gastrointestinal toxicity, and low liver and renal toxicities. Only peripheral neuropathy occurred at a higher rate in the combination arm.
For this study, 405 patients with metastatic breast cancer previously treated with anthracycline and taxanes were randomly assigned at a 2:1 ratio to receive utidelone 30 mg/m2/day intravenously on days 1 to 5 plus capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 or capecitabine 1250 mg/m2 orally twice daily on days 1 to 14 alone given every 21 days.
Approximately 80% of patients in both arms had received more than 2 prior chemotherapy regimens. A median of 6 cycles (range, 0-29) of utidelone plus capecitabine and 5 cycles (range, 0-24) of capecitabine alone were administered. Study discontinuation due to treatment-emergent adverse events was 7.9% in the utidelone arm and 6.8% in the capecitabine alone arm.
The combination of utidelone with capecitabine was superior to capecitabine alone for both progression-free survival, the primary end point (HR, 0.47; 95% CI, 0.35-0.64; log-rank P < .001), and the confirmed objective response rate by investigator, 38.1% vs 25.9% (P = .014). The clinical benefit rate was 44.6% in the utidelone arm and 32.8% in the capecitabine alone arm (P = .025).
Grade 3/4 adverse events included peripheral sensory neuropathy (18.0% in the combination arm vs 0.8% in the capecitabine alone arm), hand-foot syndrome (11.3% vs 6.8%, respectively), nausea (1.5% vs 1.5%), hyperbilirubinemia (0% vs 1.5%), diarrhea (6.0% vs 1.5%), anemia (3.4% vs 2.3%), leukopenia (4.5% vs 5.3%) and neutropenia (7.1% vs 6.8%).
Overall survival data are anticipated to be available by 2017; early analysis suggests median overall survival to date of 16.13 months (95% CI, 13.08-NE) in the utidelone arm compared with 11.60 months (95% CI, 10.02-14.69) in the capecitabine alone arm (log-rank P = .019). However, further follow-up and evaluation is required, he concluded.
1. Xu B, Sun T, Zhang Q, et al. Randomized phase III trial of utidelone, a genetically engineered epothilone analog, in combination with capecitabine versus capecitabine alone for metastatic breast cancer patients with previous taxane and anthracycline treatment. Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.