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Patients with high-risk operable breast cancer do not have significantly longer disease-free survival when treated with doxorubicin plus paclitaxel followed by weekly paclitaxel as compared with the standard regimen of doxorubicin plus cyclophosphamide followed by paclitaxel, according to updated phase III trial results.
Dr. David M. Loesch, of the Central Indiana Cancer Center in Indianapolis, reported disease-free survival in the doxorubicin (Adriamycin) plus paclitaxel (Taxol) arm (AP/T) was 81% at 5 ears. It was 80% on the doxorubicin plus cyclophosphamide arm (AC/T), with a P value no longer significant at .38 for the trial's primary end point.
Overall survival, a secondary end point, was better with AP/T, however. At 5 years, 89% of women randomized to AP/T were alive vs. 86% of those sent to AC/T (P = .054). Moreover, 83 of 106 deaths in the AC/T arm and 63 of 80 deaths in the AP/T arm were from breast cancer.
In 2004 the trialists had reported a 3-year disease-free survival rate of 88% in 915 women randomized to AP/T vs. 85% in 915 women randomized to AC/T (hazard ratio 0.74, P = .05).
Bristol Myers Oncology supported the study. Patients received AP every 3 weeks for four cycles followed by paclitaxel once a week for 12 weeks or AC every 3 weeks for four cycles followed by paclitaxel once every 3 weeks for four cycles. Patient characteristics, including hormone receptor status, and nodal involvement, were balanced.
An unplanned subgroup analysis found women with triple-negative disease (estrogen-receptor, progesterone-receptor, and HER2 negative) did better with AP/T. Their 5-year disease-free survival was 79% and overall survival 87% with AP/T vs. 74% and 79%, respectively, with AC/T.
Cardiac and hematologic toxicities were comparable. Dr. Loesch reported significantly more grade 2/3 neuropathy with AP/T, however: 32%, vs. 17% with AC/T (P less than .01).
He concluded that AP/T can be considered a standard adjuvant treatment for high-risk breast cancer and said further studies are warranted in patients with triple-negative disease.
Discussant Dr. Robert W. Carlson, professor of medicine at Stanford (Calif.) University, noted, however, that the trial failed to meet its primary end point and, thus, must be considered a negative trial. He added that the subset analysis must, by its nature, be interpreted with caution. "While the results of this trial are encouraging in women with triple-negative breast cancer, the study is insufficient in and of itself to prove superiority, and thus change practice," Dr. Carlson said.
Loesch D.M. et al. A randomized, multicenter phase III trial comparing doxorubicin + cyclophosphamide followed by paclitaxel or doxorubicin + paclitaxel followed by weekly paclitaxel as adjuvant therapy for high-risk breast cancer. Abstract 517.
Commentary |
Recently, retrospective subset analysis has suggested that women with triple-negative breast cancers, or those whose tumors overexpress HER2, are the primary beneficiaries of changes in dosage or schedule, or of the addition of taxanes to standard anthracycline-based chemotherapy. With 5 years of follow-up, this study showed no difference in outcome between a more taxane-intensive regimen and standard doxorubicin-cyclophosphamide-paclitaxel adjuvant chemotherapy, despite the suggestion of benefit at 3 years of follow-up. A hint of benefit was seen in a retrospective analysis of the triple-negative subset. This study demonstrates two important lessons of recent trials. First, mature follow-up is required in most settings to make a rational assessment of benefit versus risk. Second, current and future clinical trials in breast cancer must focus on biologic subtypes in order to assess potential benefits of new or improved therapy. — Hope S. Rugo, M.D.
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