SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.
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Dr. Marion van Mackelenbergh
Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.
According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).
To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.
The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.
Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).
Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).
Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).
No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.
“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.
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Dr. Priyanka Sharma
Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.
“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”
In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.
The investigators reported relationships with Amgen, Lilly, Pfizer, and others.
SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.