In the phase III ECOG-ACRIN E2108 trial reported in the Journal of Clinical Oncology, Seema A. Khan, MD, MPH, and colleagues found no difference in overall survival with early locoregional therapy vs continued systemic therapy among women with newly diagnosed stage IV breast cancer and an intact primary tumor site.
As stated by the investigators, “Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival, but clinical trials have reported conflicting results.”
Study Details
In the trial, patients enrolled between February 2011 and July 2015 received systemic therapy for 4 to 8 months. A total of 256 patients without disease progression were randomly assigned to receive early locoregional therapy for the primary site, including surgery and radiotherapy according to standards for nonmetastatic disease (n = 125) or continued systemic therapy (n = 131). The primary endpoint was overall survival.
Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.— Seema A. Khan, MD, MPH, and colleagues
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Systemic treatments prior to random assignment included endocrine therapy (n = 117), chemotherapy (n = 113), chemotherapy with endocrine therapy (n = 39), and chemotherapy with HER2-directed therapy (n = 105). Among patients in the locoregional therapy group, 107 received surgical treatment, including mastectomy in 75 and breast conservation in 32, with surgical margins being tumor-free in 98 (91.6%). Postoperative radiotherapy was given to 27 patients after breast-conserving surgery and 44 after mastectomy. Among patients in the continued systemic therapy group, 22 received surgery, followed by radiotherapy in 10.
Key Findings
Median follow-up was 53 months. Overall survival at 3 years was 67.9% (95% confidence interval [CI] = 58.8%–75.5%) in the continued systemic therapy group vs 68.4% (95% CI = 59.0%–76.1%) in the locoregional therapy group. Median overall survival was 53.1 months (95% CI = 47.9 months–not estimable) vs 54.9 months (95% CI = 46.7 months–not estimable), with a hazard ratio of 1.11 (90% CI = 0.82–1.52, P = .57).
The cumulative incidence of locoregional progression at 3 years was 16.3% (95% CI = 10.7%–24.4%) in the locoregional therapy group vs 39.8% (95% CI = 31.8%–49.1%) in the systemic therapy group (HR = 0.34, 95% CI = 0.21–0.56, P < .001).
Assessment of quality of life with the Functional Assessment of Cancer Therapy–Breast (FACT-B) Trial Outcome Index showed a significant difference favoring the systemic therapy group at 18 months, with no significant differences observed at any other time points. Assessment of items related to arm and chest wall symptoms and worry about primary tumor recurrence or progression showed no significant differences between groups in symptoms, worry, or functionality.
The investigators concluded, “Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.”
Dr. Kahn, of Northwestern University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from The National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
