CHICAGO – The survival impact of resecting the primary tumor in women with de novo stage IV breast cancer depends on receipt of and response to prior systemic therapy, suggested a pair of studies reported at the annual meeting of the American Society of Clinical Oncology.
A randomized trial conducted in Turkey found that, relative to peers who received initial systemic therapy, women who underwent initial resection of the primary tumor had a one-third lower risk of death at 5 years. But a prospective registry study conducted in the United States found that elective resection after a response to first-line therapy did not significantly improve overall survival, with patients living roughly 6 years regardless of whether they had the surgery or not.
Findings in context
“I think these studies have just confirmed what we know, and that is that tumor biology is critical,” said invited discussant Elizabeth A. Mittendorf, MD, PhD, of University of Texas MD Anderson Cancer Center, Houston. “Patients who do not respond to systemic therapy will do poorly, so I don’t think it’s unwise to consider a biologic ‘stress test’ with initiation of first-line therapy, knowing that patients who do not respond will not benefit from surgery.”
Those with hormone receptor–positive or HER2-positive disease are most likely to benefit from targeted therapy and may see even higher response rates as novel targeted agents are introduced. “But despite the increase in response to therapy, we really have no data at this time to suggest any benefit from surgery,” she added. “There may be some utility in continuing to enroll these patients in a clinical trial. I would suggest that it would need to be a subtype-specific trial and would question whether we have the appetite to conduct such a study.”
More information on managing de novo stage IV breast cancer is expected from ongoing trials such as the Eastern Cooperative Oncology Group’s 2108 trial, which is randomizing patients having a response or stable disease with first-line therapy to either early local therapy or delayed local therapy only at the time of progression, according to Dr. Mittendorf.
Poor accrual necessitated redesign of the trial. “As part of that redesign, there was a decrease in the target enrollment, which causes me concern that the trial will not be powered to inform its primary endpoint of overall survival,” she commented. However, “it’s interesting to note that in early 2014, shortly after the report of the trials from India and Turkey at the San Antonio Breast Cancer Symposium, there was a significant increase in enrollment, suggesting that this is a clinically important question.”
Turkish study: MF07-01
He and his colleagues enrolled in the trial women with de novo stage IV breast cancer whose primary tumor was amenable to complete surgical resection and who were healthy enough to be treated.
The women were randomized evenly either to initial systemic therapy followed by local therapy only if local progression occurred, or to initial local therapy, consisting of surgery with or without radiation therapy of the breast and axilla, followed by systemic therapy.
Among the 274 evaluable women having a median follow-up of about 40 months, the 3-year rate of overall survival did not differ significantly between the two groups, Dr. Soran reported.
However, the 5-year rate of overall survival was 41.6% in the initial surgery group and 24.4% in the initial systemic therapy group, a difference translating to a significant reduction in the risk of death (hazard ratio, 0.66; P = .005). Median survival was 46 months and 37 months, respectively.
The benefit was similar in women whose tumors had hormone receptors, whose tumors were negative for HER2, and who were younger than age 55. There was no significant benefit of up-front surgery for women with bone-only metastases, “but we believe that when we follow these patients longer, the difference is going to be statistically significant,” he said.
On the other hand, there was a trend among women who had multiple pulmonary and/or liver metastases whereby they were more likely to die if they initially had surgery instead of systemic therapy.
Locoregional progression/relapse occurred in 1% of the initial surgery group but 11% of the initial systemic therapy group. Among women who did not have locoregional progression/relapse, surgery still had a survival benefit (HR, 0.61; P = .001).