As reported in the Journal of Clinical Oncology by Filho et al, 12-year follow-up of the CALBG (Alliance) C9741 trial has shown a sustained advantage of adjuvant dose-dense vs conventional chemotherapy in disease-free and overall survival in patients with node-positive breast cancer.
Study Details
In the U.S. phase III trial, patients were randomly assigned to receive dose-dense (concurrent or sequential every 2 weeks; n = 988) or conventional (concurrent or sequential every 3 weeks; n = 985) adjuvant chemotherapy. A total of 636 patients in the dose-dense group and 640 in the conventional group had estrogen receptor (ER)-positive disease. The outcomes of interest in the extended analysis were disease-free survival and overall survival. Outcomes were also assessed according to the sensitivity to endocrine therapy (SET2,3) test index, a marker of endocrine transcriptional activity, in a total of 682 patients with ER-positive disease.
Key Findings
After a median follow-up of 12 years, patients in the dose-dense group had significantly improved disease-free survival (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.66–0.90) and overall survival (HR = 0.80, 95% CI = 0.67–0.95) vs patients in the conventional group.
Disease-free survival benefits of dose-dense chemotherapy were observed in both ER-positive patients (HR = 0.80, 95% CI = 0.65–0.98) and ER-negative patients (HR = 0.70, 95% CI = 0.55–0.90), with no significant interaction between treatment group and ER status.
According to the investigators, low SET2,3 status was highly prognostic overall, but it was also associated with improved outcomes in the dose-dense group (P for interaction = .0998 for disease-free survival and .027 for overall survival) independent of menopausal status. Overall, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not.
The investigators concluded: “At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER[-positive] breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.”
Otto Metzger Filho, MD, of Dana-Farber/Partners Cancer Care, Harvard Medical School, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Breast Cancer Research Foundation, National Institutes of Health, and others. For full disclosures of the study authors, visit ascopubs.org.
