Chinese Trial Adds Utidelone to Capecitabine in Heavily Pretreated Patients With Metastatic Breast Cancer
In a Chinese phase III trial reported in The Lancet Oncology, Zhang et al found that adding the epothilone analog utidelone to capecitabine prolonged progression-free survival in women with heavily pretreated metastatic breast cancer refractory to both anthracycline and taxane treatment.
Study Details
In this open-label trial, 405 patients from 26 sites in China were randomized 2:1 between August 2014 and December 2015 to receive 21-day cycles of utidelone at 30 mg/m² intravenously once per day on days 1 to 5 plus capecitabine at 1,000 mg/m² twice per day on days 1 to 14 (n = 270) or capecitabine alone at 1,250 mg/m² twice per day on days 1 to 14 (n = 135) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival assessed by an independent radiology review committee in the intent-to-treat population.
In the combination vs control groups: median age was 50 years in both (12% and 13% ≥ 60 years); 26% and 27% had HER2-positive and 63% and 59% hormone receptor–positive disease; 16% and 8% had received anti-HER2 treatment; 54% and 53% had received endocrine treatment; the median number of prior chemotherapy regimens was 2 (range = 1–6) and 2 (range = 1–5), with 39% and 41% receiving at least 3 prior regimens; and 10% and 16% had received prior capecitabine.
Progression-Free Survival
Median follow-up for progression-free survival was 6.77 months in the utidelone plus capecitabine group and 4.55 months in the capecitabine alone group. Median progression-free survival was 8.44 months vs 4.27 months (hazard ratio [HR] = 0.46, P < .0001). Partial response was observed in 40% (complete response in one patient, < 1%) vs 21%, and median response duration was 7.59 vs 5.62 months. Overall survival data were immature at the time of analysis; at data cutoff, median overall survival was 16.13 months vs 12.78 months (HR = 0.63, P = .0059).
Toxicity
Peripheral neuropathy was the most common grade 3 adverse event in the combination group (22% vs < 1%), and palmar-plantar erythrodysesthesia was the most common adverse event in the capecitabine alone group (8% vs 7%). Peripheral sensory neuropathy led to discontinuation of utidelone in 16% and capecitabine in 10% of the combination group. Serious adverse events occurred in 16 patients in the combination group, with diarrhea being the most common (3 patients) and 14 patients in the control group, with diarrhea, increased blood bilirubin, and anemia occurring in 2 patients each. One death in the combination group, due to pericardial effusion, and one in the control group, due to dyspnea, were considered at least possibly related to study treatment.
The investigators concluded: “Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer.”
The study was funded by Beijing Biostar Technologies.
Binghe Xu, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
