• Oncology Clinical Trials
• Breast Cancer
• Adjuvant/Neoadjuvant Therapy

• Oncology Clinical Trials
• Oncology
• Breast Cancer
• Adjuvant/Neoadjuvant Therapy

Amir Sonnenblick, MD, PhD, Free University of Brussels, Brussels, Belgium, presented data from the 10-year final safety and efficacy analyses of the Intergroup Phase 3 Trial to Evaluate the Activity of Docetaxel, Given Either Sequentially or in Combination With Doxorubicin, Followed by Cyclophosphamide, Metho-trexate, and Fluorouracil (CMF), in Comparison to Doxorubicin Alone, or in Combination With Cyclophosphamide, Followed by CMF, in the Adjuvant Treatment of Node-Positive Breast Cancer Patients [BIG 2-98; NCT00174655]. The results demonstrated that the addition of docetaxel to anthracycline-based adjuvant chemotherapy may benefit patients with estrogen receptor (ER)-positive breast cancer.

According to Prof Sonnenblick, adding taxanes to an anthracycline-based chemotherapy regimen in the adjuvant setting has become a standard approach in the management of patients with breast cancer. However, long-term outcomes data are still lacking regarding the safety and efficacy of this approach.

This trial randomized 2887 patients with lymph node-positive breast cancer to 1 of 4 treatment arms:

• Arm A: Sequential control—doxorubicin (75 mg/m²) for 4 cycles, followed by CMF.

• Arm AC: Concurrent control—doxorubicin (60 mg/m²) plus cyclophosphamide (600 mg/m²) for 4 cycles, followed by CMF.

• Arm A-T: doxorubicin (75 mg/m²) for 3 cycles, followed by docetaxel (100 mg/m²) for 3 cycles, followed by CMF.

• Arm AT: doxorubicin (50 mg/m²) plus docetaxel (75 mg/m²) for 4 cycles, followed by CMF.

The primary objective was to determine the efficacy of docetaxel, regardless of schedule, on disease-free survival (DFS). However, after 10 years and 1072 DFS events, docetaxel treatment did not improve DFS (HR, 0.91; 95% CI, 0.81 to 1.04; P = .16) or overall survival (OS; HR, 0.88; 95% CI, 0.76 to 1.03; P = .11), compared with control arms.

Similarly, there was no significant difference in DFS (HR, 0.86; 95% CI, 0.72 to 1.03, P = .1) or OS (HR, 0.85; 95% CI, 0.68 to 1.06; P = .15) between sequential docetaxel and sequential control or in DFS (HR, 0.88; 95% CI, 0.76 to 1.02; P = .09) or OS (HR, 0.84; 95% CI, 0.7 to 1.01; P = .06) between sequential docetaxel and concurrent doxorubicin-docetaxel.

In a multivariate model, however, data showed a trend for improved DFS (HR, 0.79; 95% CI, 0.63 to 1.01; P = .05) and OS (HR, 0.76; 95% CI, 0.57 to 1.01; P = .06) in patients with ER-positive breast cancer with high levels of Ki67 proliferation marker (≥ 14%) who were treated with docetaxel.

There were no significant long-term safety issues. Grade 3 to 4 cardiac toxicity was recorded in only 4 patients, and long-term treatment-related neurotoxicity occurred in only 1.6% and 1.0% of patients in the docetaxel- and non-docetaxel-based regimens, respectively.

Although the addition of docetaxel to anthracycline-based adjuvant chemotherapy did not improve DFS or OS, the data suggested a benefit of sequential docetaxel in patients with highly proliferative ER-positive breast cancer, concluded Prof Sonnenblick.

• © 2014 MD Conference Express®