SABCS 2018: Does Adjuvant Capecitabine Improve Outcomes in Early-Stage Triple-Negative Breast Cancer?
Treating patients with early-stage triple-negative breast cancer with capecitabine after surgery and standard chemotherapy did not significantly improve disease-free or overall survival compared with observation, according to data from the randomized, phase III GEICAM/CIBOMA clinical trial presented by Martín et al at the 2018 San Antonio Breast Cancer Symposium (Abstract GS2-04).
“Patients with early-stage triple-negative breast cancer are usually treated with surgery and chemotherapy, and sometimes radiotherapy,” said first author Miguel Martín, MD, PhD, Professor of Medicine and Head of the Medical Oncology Service at Hospital Gregorio Marañón, Universidad Complutense in Madrid, in a statement. “New therapeutic approaches are urgently needed, however, because the risk of relapse is high: relapse is seen in 7% to 10% of those with stage I disease, 15% to 20% of those with stage II disease, and 25 to 50% of those with stage III disease.
“We were disappointed to find that adding adjuvant capecitabine to the standard treatment did not significantly improve disease-free or overall survival,” continued Martín. “However, given that we found a subset of patients with nonbasal-like disease who seemed to have a significant benefit from capecitabine, and data from the CREATE-X trial showed that adjuvant capecitabine significantly reduced the rate of relapse and improved overall survival when administered to [patients with] breast cancer … with residual disease after neoadjuvant chemotherapy, we strongly recommend that patients with triple-negative breast cancer discuss adjuvant capecitabine with their oncologists.”
Study Findings
Dr. Martín and colleagues randomly assigned 876 patients with early-stage triple-negative breast cancer who had been treated with surgery and chemotherapy in the trial to 8 cycles of capecitabine or observation. After a median follow-up of 7.3 years, the 5-year disease-free survival rate was 79.6% among the 448 patients randomly assigned to be treated with capecitabine and 76.8% among the 428 patients randomly assigned to observation. The improvement in 5-year disease-free survival was not statistically significant, noted Dr. Martín.
“There was a nonsignificant trend in favor of capecitabine, but the trial had only 876 participants, which means it was not statistically powered to identify small but clinically relevant differences,” noted Dr. Martín. “One possible reason for the discrepancy in the results of the CREATE-X trial and our trial may be that the populations had different prognostic features; the risk of relapse of our population was much less than in the CREATE-X trial.”
In subgroup analyses, Dr. Martín and colleagues found that among the 248 patients with nonbasal-like disease, as defined by immunohistochemistry, those randomly assigned to adjuvant capecitabine were 49% less likely to experience a disease event and 52% less likely to die compared with those assigned to observation.
“This is an intriguing finding,” said Dr. Martín. “However, it should be interpreted with caution because the interaction test was negative for disease-free survival (P = .0694), although it was statistically significant for overall survival (P = .0052).”
Similar results were found for overall survival (basal hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.81–1.77, P = .3684; nonbasal HR = 0.48, 95% CI = 0.26–0.91, P = .0205; interaction P = .0155).
According to Dr. Martín, the main limitation of the study is the limited power of the trial to show small but clinically relevant improvements in outcome with capecitabine due to the sample size and the lower-than-expected number of relapse events in the control arm.
Disclosure: This study was supported by Roche. See the study authors’ full disclosures at sabcs.org.
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