Phase III Trial Finds XP as Efficacious as EP as First-Line Therapy for Metastatic Breast Cancer

ASCO — Capecitabine (Xeloda)/paclitaxel (XP) is at least as efficacious as epirubicin (Ellence)/paclitaxel (EP) as first-line therapy for metastatic breast cancer, data from a randomized, multicenter phase III trial show, Hans-Joachim Lck, MD, PhD, of the Horst Schmidt Klinik, Wiesbaden, Germany, reported at the American Society of Clinical Oncology 2006 Annual Meeting (abstract 517). Because anthracyclines are being increasingly used in the adjuvant setting, non-anthracycline-containing regimens are needed in the metastatic setting, Dr. Lck said. Earlier research that he and his coinvestigators in the AGO Breast Cancer Study Group conducted has shown that increasing the dose of epirubicin in the metastatic setting does not improve outcomes, he added.

The 340 participants in the noninferiority trial were women with metastatic breast cancer whose metastases were not limited to bone and who had not received chemotherapy for metastases. The patients were randomized to treatment on 21-day cycles with EP (epirubicin 60 mg/m² on day 1 and paclitaxel 175 mg/m² on day 1) or XP (capecitabine 1,000 mg/m² twice daily on days 1 to 14 and paclitaxel 175 mg/m² on day 1). Patients could receive up to six cycles. "To our knowledge, this is the first trial to compare an anthracycline combination with a nonanthracycline combination in this period of treatment," he noted. By intention-to-treat analysis, median progression-free survival did not differ significantly between the EP and XP arms (11.1 vs 12.0 months, respectively), Dr. Lck said; moreover, the response rates (complete and partial responses) were almost identical (51% vs 52%). Median overall survival was also statistically indistinguishable (24.0 vs 25.6 months).

Patients who received EP had a comparatively higher incidence of grade 3-4 leukopenia (41% vs 12%) and neutropenia (52% vs 38%); XP patients had a comparatively higher incidence of grade 3-4 diarrhea (5% vs<1%) and hand-foot syndrome (12% vs 0%). "A dose reduction in capecitabine per protocol in patients who developed these toxicities makes it possible to go further with the treatment without problems," Dr. Lck said. He added that the intensified education for investigators and nurses on how to handle hand-foot syndrome may have contributed to the relatively low rate seen in the study. Quality-of-life data are still being analyzed, but a comparison of ECOG performance status during treatment, as a general indicator, showed no difference between the two groups.

"Capecitabine/paclitaxel is an active treatment in metastatic breast cancer. This treatment is feasible. The toxicity is in the expected range and it's manageable," Dr. Lck commented. "So in this situation, XP maybe can replace anthracycline-containing regimens as a first-line option in high-risk or symptomatic metastatic breast cancer patients."