Adjuvant Chemo Plus Tamoxifen Extends Disease-Free Survival in High-Risk Breast Cancer
Last Updated: 2009-12-10 18:46:17 -0400 (Reuters Health)
NEW YORK (Reuters Health) - In postmenopausal women with node-positive, endocrine-responsive breast cancer, 6 months of anthracycline-based chemotherapy before starting tamoxifen can significantly improve disease-free survival - but only in women with a high "recurrence score."
These results, reported by a single team of investigators, appear in two separate studies: one published in The Lancet and the other in The Lancet Oncology.
The first study, by Dr. Kathy S. Albain, from Loyola University Stritch School of Medicine in Maywood, Illinois, and associates, was released early online December 10th by The Lancet to coincide with the researchers' presentation at the CTRC-AACR San Antonio Breast Cancer Symposium.
It describes data from 9 years' follow-up of the phase III Southwest Oncology Group (SWOG)-8814 clinical trial. The initial intention-to-treat analysis had included 1477 women who were randomly assigned to one of three groups: tamoxifen alone (n=361); cyclophosphamide, doxorubicin and fluorouracil (CAF) followed by tamoxifen (n=566); or CAF with concurrent tamoxifen (n=550).
CAF was administered every 4 weeks for 6 cycles, at "the most dose-intense combination among the commonly used regimens when this trial was designed," the authors said. Tamoxifen was given for 5 years.
After a median follow-up of 8.94 years (maximum, 13 years), disease-free survival was significantly longer in the two CAF plus tamoxifen groups than in the tamoxifen-alone group (p = 0.002). Actuarial 10-year disease-free survival was 57% for the combination groups vs 48% for the tamoxifen-alone group (adjusted hazard ratio 0.76, p=0.002).
Overall survival was also significantly longer in the two CAF-tamoxifen groups, though the adjusted HR did not reach statistical significance (0.83, p=0.057). Kaplan-Meier survival curves first diverged after the fourth year, remaining separate from then on.
The absolute risk reduction at 10 years with CAF plus tamoxifen was 5% (survival 65% vs 60%).
Sequential CAF and tamoxifen was marginally superior to concurrent treatments (10-year estimates, 60% vs 53%, p = 0.55). Overall survival did not differ significantly.
However, as Drs. Michael Gnant and Guenther G. Steger from Medical University of Vienna, Austria, remark in a commentary, "There is a price to pay for a 5% overall survival benefit," in terms of adverse events.
Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukemia occurred more often in the CAF plus tamoxifen groups than in the tamoxifen-alone group.
The second major finding - that the benefit of adjuvant chemotherapy was limited to patients at higher risk for recurrence - is reported in The Lancet Oncology, which was also released today.
Dr. Albain and her associates used a 21-gene recurrence score assay (Oncotype DX) designed for use in patients with node-negative, estrogen-receptor-positive breast cancer, and treated with tamoxifen.
Using this assay on 367 stored specimens from the SWOG-8814 subjects (148 from the tamoxifen group and 219 from the CAF-tamoxifen group), they determined patients' recurrence scores and then assessed the affect of these scores on disease-free survival by treatment group.
"The recurrence score was a strong predictive factor of benefit from CAF for disease-free survival...but degree of CAF benefit depended on the recurrence score," the researchers report. They saw no benefit for scores less than 18 (on a scale of 0 to 100), whereas there was a significant benefit with scores of 31 or more.
Specifically, they add, for women with higher scores, 10-year disease-free survival with or without CAF was 55% vs 43%, respectively. By contrast, 10-year disease-free survival rates with or without CAF were 64% and 60%, respectively.
Similar differences were seen for overall 10-year survival.
Dr. Albain and her colleagues conclude that "for postmenopausal women with few comorbidities who have a substantial risk of recurrence or death based on the prognostic profile of their tumor, the risk benefit balance favors anthracycline-based chemotherapy followed by tamoxifen."
Lancet and Lancet Oncol, 2009.
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