Weekly paclitaxel or docetaxel every 3 weeks extended DFS in breast cancer

Issue: January 10, 2015

SAN ANTONIO — Women with axillary node-negative or high-risk node-negative breast cancer achieved prolonged DFS and marginally improved OS when they received adjuvant paclitaxel every week or docetaxel every 3 weeks compared with paclitaxel every 3 weeks, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

Further, weekly paclitaxel extended DFS and OS in women with triple-negative breast cancer, whereas docetaxel administered every 3 weeks improved DFS in women with ER-positive, HER-2–negative disease.

Joseph A. Sparano

Joseph A. Sparano, MD, professor of medicine and women's health at Albert Einstein College of Medicine, and colleagues evaluated various regimens in 4,954 women with axillary node-positive or high-risk node-negative breast cancer. Previously released results, based on a median 5.3 years of follow-up, showed those who received adjuvant weekly paclitaxel (HR=0.73; P=.0006) or docetaxel every 3 weeks (HR=0.77; P=.02) demonstrated longer DFS than women who received paclitaxel every 3 weeks.

The current analysis occurred after a median 12.1 years of follow-up. The numbers of DFS events (1639 vs. 1048) and deaths (1283 vs. 686) in the current analysis vs. the previous report were substantially higher.

All patients received four cycles of 60 mg/m² doxorubicin and 600 mg/m² cyclophosphamide every 3 weeks. Patients who were ER-positive also received endocrine therapy for 5 or more years.

The standard arm consisted of 175 mg/m² paclitaxel every 3 weeks for four cycles (P3). This arm was compared with 80 mg/m² paclitaxel weekly for 12 weeks, 100 mg/m² docetaxel every 3 weeks for four cycles, or 35 mg/m² docetaxel weekly for 12 weeks.

Overall, the taxane and schedule alone were not significantly associated with outcomes; however, the taxane and schedule interaction was significantly associated with DFS (P˂.001) and OS (P=.007).

Weekly paclitaxel was associated with improved DFS (HR=0.84; 95% CI, 0.73-0.96) and marginally improved OS (HR=0.87; 95% CI, 0.75-1.02) compared with the standard arm. Docetaxel every 3 weeks also was associated with improved DFS (HR=0.79; 95% CI, 0.68-0.9) and OS (HR=0.86; 95% CI, .73-1).

“For the weekly paclitaxel arms, the results are qualitatively similar, but quantitatively less than the original report,” Sparano said. “The hazard ratios were in the 0.76 to 0.79 range initially, and are now in the range of 0.84 to 0.87.”

Patients with triple-negative breast cancer (n=1,025) demonstrated improved 10-year DFS (HR 0.69; P=0.01) and 10-year OS (HR 0.69; P=0.019) when they received weekly paclitaxel.

Among patients with ER-positive, HER-2–negative breast cancer (n=2,785), docetaxel administered every 3 weeks conferred prolonged DFS (HR 0.76; P=0.004) without an OS benefit (HR 0.87; P=.2). Results also demonstrated inferior OS in this subtype was associated with black race (HR=1.6; P=.002) and obesity (HR 1.23; P=.009). Obesity also was associated with a greater risk for recurrence 3 to 8 years after diagnosis.

“For ER-positive, HER-2–negative disease, the trend for improved outcomes with experimental taxane arms seen at 5 years was not consistently observed at 10 years,” Sparano said. “This suggests attention to extended adjuvant endocrine therapy may be more relevant in this patient population that is at risk for late relapse than the type or dose schedule of taxane administered.”

For more information:

Sparano JA. Abstract #S3-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.

Disclosure: The researchers report no relevant financial disclosures.