Adding Taxane to Anthracycline-Based Therapy Does Not Improve Outcomes

SAN ANTONIO—Giving a taxane following standard anthracycline-based chemotherapy for early breast cancer will not improve outcomes, suggest results of a 104-center, British study presented at the San Antonio Breast Cancer Symposium. “There was no difference with regard to the primary endpoint of disease-free survival at five years,” said Paul Ellis, MD, Head of Medical Oncology at Guy's and St. Thomas' National Health Service Trust and Medical Director for the South East London Cancer Network in London, the principal investigator of TACT, the Taxotere as Adjuvant Chemotherapy Trial. Additionally, there was also no difference in the overall survival rate between the patients who received the taxane docetaxel following anthracycline-based therapy and those who did not receive docetaxel. And, as expected, Dr. Ellis said, women receiving docetaxel experienced more serious toxicities than those who were not given a taxane. The report was the first efficacy results of the study, which he said is the largest of the primary taxane studies to date. Thirteen previous trials of taxane-based adjuvant chemotherapy have had inconsistent results, with about half finding a benefit for adding taxanes and about half showing no benefit, he noted. Earlier studies that showed a benefit for anthracycline-based treatment followed by taxanes left open the question of whether the benefit was due to the taxanes or the increased duration of therapy. The new trial was designed so that all patients would have eight cycles of treatment. Dr. Ellis and his co-researchers recruited 4,162 women with operable, histologically confirmed, completely resected, early invasive breast. Reflecting standard UK practice, physicians at participating centers chose one of two regimens as their control arm. A total of 1,265 women were randomized to receive eight cycles of fluorouracil (5-FU), the anthracycline epirubicin, and cyclophosphamide (FEC). Another 824 women were given four cycles of epirubicin followed by four cycles of cyclophosphamide, methotrexate, and 5-FU (E-CMF). The remaining 2,073 patients were randomized to four cycles of FEC, followed by four cycles of docetaxel. Nearly all the women with estrogen receptor-positive disease received tamoxifen, followed in nearly one-third of cases by an aromatase inhibitor. About 9% of patients with HER2-positive tumors received trastuzumab. Study Results At a median of 51.8 months of follow-up, five-year results showed that 74.7% of women in the taxane arm were alive and free of disease at five years, compared with 73.9% in the control arms, a nonsignificant difference. Similarly, the overall survival rates were 82% and 81.8%. All but 40 deaths among women in the trial were preceded by a recurrence of breast cancer, Dr. Ellis said. A total of 291 women in the taxane arm died of breast cancer, compared with 301 women in the control arms. As seen in other large docetaxel trials, there was a significantly higher rate of Grade 3 and 4 neutropenia and febrile neutropenia in the taxane arm. Other side effects experienced by significantly more women in the taxane arm included lethargy, stomatitis, and musculoskeletal complaints. When the researchers performed subgroup analyses according to biomarker status, “there was no suggestion of benefit in women with estrogen receptor-positive disease,” which was the majority of patients, Dr. Ellis said. There was a trend toward improvement in the disease-free survival rate among women who had estrogen receptor-negative and HER2-positive disease, but the figure did not reach significance, he said. The study was supported by Cancer Research UK, Pfizer, Roche, and Sanofi-Aventis. ‘Maybe Should Not Be Treating Everyone the Same Way’ During the question-and-answer period, Kathleen I. Pritchard, MD, Head of Clinical Trials and Epidemiology at Toronto Sunnybrook Regional Cancer Centre and a Professor of Medicine at the University of Toronto, noted that in the National Cancer Institute of Canada MA.21 trial, a regimen of doxorubicin/cyclophosphamide followed by the taxane paclitaxel was much less effective “than the dose-intense regimen we use in Canada”—that is, dose-dense epirubicin/cyclophosphamide followed by paclitaxel.Figure: Paul Ellis, MD: “Earlier studies that showed a benefit for anthracycline-based treatment followed by taxanes left open the question of whether the benefit was due to the taxanes or the increased duration of therapy.”The value of the addition of taxanes to various regimens “depends very much on the efficacy of the control regimen,” she said. Dr. Ellis replied, “I'm not saying that taxanes are not a good option. But maybe we should not be treating everyone the same way.” Asked to comment, Session Co-Moderator Lisa A. Carey, MD, Medical Director of the University of North Carolina Breast Center, said that given that some studies have shown a benefit for taxanes, TACT has to be placed “in the context of the body of evidence.” The findings, while seemingly negative, are actually reassuring, she added, “highlight[ing] that there are a number of active regimens we can offer our patients. This gives us some reassurance that you don't have to include a taxane in the regimen if there are reasons you wouldn't want to, such as in a patient with diabetic neuropathy.”

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