Shorter FEC + Pac Ups DFS in Breast Ca

SAN ANTONIO—Marked reductions in breast cancer recurrence were achieved with a shorter standard adjuvant chemotherapy regimen, augmented by weekly doses of paclitaxel, in a study by the Spanish Group for Breast Cancer Research, the GEICAM 9906 trial, presented at the 28th Annual San Antonio Breast Cancer Symposium (abstract 39).

The first interim analysis also showed an improvement in disease-free survival (DFS), and similar benefits in all subgroups, according to Miguel Martin, MD, PhD, of Hospital Universitario San Carlos, Madrid, Spain.

GEICAM 9906 included 1,248 patients with operable breast cancer randomized to the experimental arm—four cycles of fluorouracil (600 mg/m2), epirubicin (90 mg/m2), and cyclophosphamide (600 mg/m2) (FEC) followed by paclitaxel 100 mg/m2 weekly for 8 weeks—or to FEC given for six cycles, a standard adjuvant regimen. Total treatment duration was 15 weeks for the experimental regimen vs 17 weeks for the standard arm.

Additionally, tamoxifen was given for 5 years to women with hormone-receptor-positive tumors (76% to 82%), and radiotherapy was administered according to the individual center's guidelines (70% to 71%).

The interim analysis was triggered after 211 recurrences, with a median follow-up of 46 months. Of these 211 events, 128 were in the control arm and 83 in the experimental arm. Breast cancer relapses accounted for 120 and 68 of these, respectively; second malignancies and contralateral breast cancers numbered 7 and 11; and deaths from other causes totaled 1 and 4, respectively.

These outcomes yielded a disease-free survival rate of 79% vs 85%, respectively. FEC plus paclitaxel resulted in a 37% reduction in the risk of recurrence, after controlling for nodes, age, tumor size, histology, hormone-receptor status, and tamoxifen use. This difference was highly significant (P = .0008), Dr. Martin said.

"FEC followed by paclitaxel did better in all subgroups of patients," he said. Subsets included patients with 1 to 3 positive nodes and 4+ positive nodes, pre- and postmenopausal status, hormone-receptor-positive and hormone-receptor-negative status, and HER2 3+ and 0 to 2+ positivity.

He emphasized that the experimental approach was almost equally effective in patients whether they were hormone-receptor-positive or hormone-receptor-negative; hazard ratios in these populations were 0.65 and 0.50, respectively.

A trend emerged for an improvement in overall survival with FEC/paclitaxel, with 94% of patients alive at 46 months, compared with 92% on standard FEC, though the difference is not yet statistically significant. The combined approach yielded a relative risk of 0.74.

Hematologic toxicity was slightly higher with the longer FEC-only regimen, with neutropenia grades 3-4 in 26% vs 21%, and febrile neutropenia in 9% and 5%; anemia occurred in 1% of each group. In terms of nonhematologic toxicity, the paclitaxel arm had more neuropathy (4% vs 0%) and asthenia (6% vs 2%). Cardiovascular toxicity grade 2 or higher was uncommon and similar between the arms, except for more thrombosis/embolism in the paclitaxel arm (4 patients vs 2). Altogether, cardiovascular toxicity occurred in 10 patients on FEC followed by paclitaxel and in 5 patients treated with FEC only.

Dr. Martin predicted that "after this study, and others being conducted by ECOG and by French investigators, I believe the new standard [in node-positive breast cancer] will be three or four courses of FEC followed by either of the taxanes."

'A Great Study'

Frankie Holmes, MD, of US Oncology, Houston, congratulated the investigators on "a great study." She said the study addressed the vexing issue of whether to give taxanes to patients who are ER positive. "This study had a large number of ER-positive patients, and it is unabashedly positive," she said.