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Adjuvant capecitabine fails to extend survival in early-stage triple-negative breast cancer
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SAN ANTONIO — Adjuvant capecitabine did not prolong DFS or OS among women with early-stage triple-negative breast cancer who underwent surgery and standard chemotherapy, according to results from the randomized phase 3 GEICAM/CIBOMA trial presented at San Antonio Breast Cancer Symposium.
However, researchers observed a statistically significant increase in DFS and OS among a subset of patients with a nonbasal-like disease.
“Our trial shows that capecitabine could be appropriate therapy for a subset of patients with triple-negative breast cancer, however, I would not recommend clinicians to make decisions based off our study as it is now. More research is needed to confirm the benefit we observed in patients with non-basal like disease,” researcher Miguel Martín, MD, PhD, professor of medicine and head of the medical oncology service at Hospital Gregorio Marañón at Universidad Complutense in Madrid, told HemOnc Today.
Patients with triple-negative breast cancer are sensitive to chemotherapy, but a significant proportion of these patients eventually relapse after conventional treatment. New treatment approaches are needed for this patient population, Martin said.
Results of the CREATE-X trial showed adjuvant capecitabine significantly reduced relapse risk and improved OS among patients with HER2-negative primary breast cancer who have residual disease after neoadjuvant chemotherapy.
Martin and colleagues conducted a randomized trial that included 876 women with stage I to III triple-negative breast cancer who underwent surgery and chemotherapy.
Researchers assigned 448 women to adjuvant oral capecitabine (1,000 mg/m2 twice daily for 14 days, administered in eight 3-week cycles). The other 428 women underwent observation.
Treatment groups were balanced with regard to age, menopausal status at diagnosis, stage at diagnosis and nodal status.
DFS served as the primary endpoint. Secondary endpoints included OS, subgroup analyses, safety and biomarker analysis.
Median follow-up was 7.34 years.
Results showed no statistically significant difference between the capecitabine and observation groups with regard to 5-year DFS (79.6% vs. 76.8%; adjusted HR = 0.79; 95% CI, 0.61-1.03) or 5-year OS (86.2% vs. 85.9%; HR =0.92; 95% CI, 0.66-1.28).
“Our trial is formally negative, as it did not reach statistical significance,” Martin said. “However, only 876 patients were included, which means it was not statistically powered to identify small but clinically relevant differences. 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 [for] relapse of our population was much less than in the CREATE-X trial.”
Subgroup analyses showed patients with nonbasal-like disease (n = 248) derived a benefit from capecitabine, appearing more likely than those assigned observation to achieve 5-year DFS (82.6% vs. 72.9%; HR = 0.53; 95% CI, 0.31-0.91) and 5-year OS (89.5% vs. 79.6%; HR = 0.42; 95% CI, 0.21-0.81) than those assigned observation.
However, Martin urged caution when interpreting these findings because the interaction test was negative for DFS (P = .0694) but statistically significant for OS (P = .0052).
“We are in conversation now with the investigators of the CREATE-X trial to try to reproduce our results,” Martin told HemOnc Today. “If the results are reproduced, we can then recommend clinicians and patients to have basal status identified, which is very easy to do and can be done in any lab. Still, for the time being, our trial is not practice changing. Stay tuned.” – by Jennifer Southall
Reference:
Martin M, et al. Abstract GS2-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 4-8, 2018; San Antonio.
Disclosures: Roche funded this study. Martin reports speakers’ honoraria from Eli Lilly and Pfizer; honoraria for participation in advisory boards from AstraZeneca, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, PharmaMar, Roche/Genentech and Taiho Oncology; and research grants from Novartis and Roche. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Matthew Goetz, MD
For years, oncologists have been treating patients who have triple-negative breast cancer and residual disease after neoadjuvant chemotherapy and considering those patients for capecitabine. This was based upon results of the CREATE-X trial.This trial by Martín and colleagues showed that, overall, capecitabine did not improve outcomes; however, researchers found an interesting subset of patients who appeared to derive some benefit. These are somewhat provocative data, but they are not yet practice changing. Certainly, one of the questions we are going to want to answer is whether there was any indication that the patients who derived benefit in the CREATE-X trial were the same subset of nonbasal-like patients who derived benefit in this study.
This study does not ‘shut the door’ for the use of capecitabine. Instead, it leads to more questions about whether there are subsets of patients who may benefit from capecitabine. In general, we are moving away from giving chemotherapy blindly to our patients. We have no idea how patients have responded to prior therapy and whether there is any value to adding any more drugs to a certain patient’s situation. For future trials in this space, we are going to have to get away from simply giving therapy to everyone before we know how they respond to treatment.
Perspective
Back to TopCarlos Arteaga, MD
Patients with triple-negative breast cancer are a very heterogeneous group. We all need additional education about this population, and there is a need for much more research. I’m not sure that [basing treatment decisions based on basal status] would be appropriate or recommended, but I think we have a duty to define this phenotype better.
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