CHICAGO―Single-agent paclitaxel did not show equivalence to doxorubicin and cyclophosphamide as adjuvant therapy for breast cancer in women with zero to three axillary nodes, according to long-term results of the Cancer and Leukemia Group B (CALGB) 40101 study at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

This conclusion “is very unlikely to change with additional follow-up,” noted Lawrence N. Shulman, MD, of Dana-Farber Cancer Institute, Boston, MA, and colleagues on behalf of the CALGB. Paclitaxel was found to be less toxic than doxorubicin and cyclophosphamide.

The investigators enrolled patients with operable breast cancer with zero to three positive nodes. The study was designed to address the superiority of six versus four cycles of therapy as well as equivalence of single-agent paclitaxel to standard doxorubicin/cyclophosphamide.

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“After enrolling 3,871 patients, the study closed in 2010 due to slowing accrual,” Dr. Shulman noted.

When the trial was activated in 2002, paclitaxel 80 mg/m2 was administered once weekly for 12 or 18 weeks and doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 was given every 3 weeks for four or six cycles. In 2003, with 570 patients enrolled, the schedules were revised to four or six cycles every 2 weeks for both paclitaxel 175 mg/m2 and doxorubicin/cyclophosphamide. The six-cycle arms were dropped in 2008, with 3,871 pts enrolled, because of slow accrual.

At a median follow-up of 6.1 years, there were 437 relapse-free survival (RFS) events. The hazard ratio (HR) of 1.26 (95% CI: 1.05-1.53; P=0.02) “did not allow a conclusion of equivalence of paclitaxel with doxorubicin/cyclophosphamide,” he said.

With 266 deaths, the HR for overall survival (OS) is 1.27 (95% CI: 1.00-1.62; P=0.05), favoring doxorubicin/cyclophosphamide. The estimated absolute advantage of doxorubicin/cyclophosphamide at 5 years is 3% (91% vs. 88%) for RFS and 1% (95% vs. 94%) for OS.

All nine treatment-related deaths occurred in patients who received doxorubicin/cyclophosphamide. Six of these patients had developed acute myeloid leukemia (AML) and one had developed myelodysplastic syndrome (MDS), all between 11 and 34 months after enrollment. The other two patients who died suffered from treatment-related cardiac toxicity.