San Antonio, TX—Although capecitabine (Xeloda) is approved for metastatic breast cancer, it is not clear whether it should be used in early breast cancer, and its optimal role remains to be established. A large meta-analysis sheds some light on this issue, demonstrating that capecitabine improves disease-free survival (DFS) and overall survival (OS) for patients with triple-negative breast cancer (TNBC) when added to other systemic therapies, but not as a substitute for other therapies.
“Capecitabine [alone] did not alter overall DFS, but when added to other systemic therapies there was an improvement. Overall survival was also improved when capecitabine was given in addition to other therapies. There is no evidence supporting a predictive value of capecitabine-specific adverse events on outcome. It can be concluded that the addition of capecitabine to other treatment may be recommended for TNBC patients,” stated lead investigator Marion van Mackelenbergh, MD, Universitätsklinikum Schleswig-Holstein, Kiel, Germany, at last year’s San Antonio Breast Cancer Symposium.
This is a “major finding,” noted Harold J. Burstein, MD, PhD, Institute Physician, Breast Oncology Program, Dana-Farber Cancer Institute, Boston, MA, in an online post. “We have undervalued this approach, because all-comers trials rarely showed a benefit.”
This meta-analysis did not compare the effects of capecitabine with carboplatin in patients with TNBC. Studies are needed in early breast cancer to compare capecitabine with other systemic therapies, including carboplatin.
New Data from >15,000 Patients
The meta-analysis included data from 15,457 patients enrolled in 12 randomized controlled trials; 7893 patients with early breast cancer received treatment with capecitabine, and 7477 patients were in the control arms. Of the studies included in the meta-analysis, 5 addressed treatment with capecitabine used instead of other therapies, and 7 evaluated capecitabine in addition to other therapies. The evaluable population for DFS totaled 4097 patients.
The analysis was performed on the overall study population, as well as on 2 predefined groups, including patients who received capecitabine in addition to other therapies and those who received capecitabine instead of another systemic treatment.
A total of 74.3% of the study patients had nodal involvement; 56% presented with stage II disease; approximately 68% had hormone receptor–positive disease; 45% had high-grade disease; and 15% had HER2-positive disease. Approximately 80% of the studies were conducted in the adjuvant setting, and almost 20% were conducted in the neoadjuvant setting.
In the overall analysis, no significant effect was seen of capecitabine on DFS. However, among patients who received capecitabine in addition to other therapies, a significant DFS benefit was observed (hazard ratio [HR], 0.888).
Benefit Limited to Patients with TNBC
“Of all the trials, only the FinXX and CREATE-X trials [in the meta-analysis] had positive results for DFS, and no benefit of capecitabine on DFS was observed when capecitabine was given instead of another treatment,” Dr van Mackelenbergh noted.
A modest OS benefit for capecitabine was observed for the total data set (HR, 0.892), and the OS benefit was more robust when capecitabine was added to other systemic therapies (HR, 0.837).
“CREATE-X was the only trial that was positive for OS. There was no OS benefit when capecitabine was substituted for another systemic therapy,” Dr van Mackelenbergh emphasized.
In patients with TNBC, capecitabine improved the OS by 22% and the DFS rate by 18% when added to standard chemotherapy (P = .004 for both). No benefit was observed in TNBC when capecitabine was given instead of another systemic therapy.
An analysis performed according to disease biologic subtype showed an overall OS benefit for capecitabine in patients with TNBC (HR, 0.828) and when capecitabine was added to other therapies in TNBC (HR, 0.778).
“Since the publication of the CREATE-X results, capecitabine has been a reasonable option for TNBC. The meta-analysis results support this. There is no benefit in the estrogen receptor–positive patients, and the benefit is limited to the TNBC population,” said Steven Isakoff, MD, PhD, Medical Oncologist, Center for Breast Cancer, Massachusetts General Hospital Cancer Center, Boston.
The most common grades 3 and 4 toxicities with capecitabine were mucositis, hand-foot syndrome, and diarrhea. No significant associations were reported between capecitabine-specific toxicities and treatment benefit.