Metronomic capecitabine maintenance extends DFS in triple-negative breast cancer
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A year of maintenance therapy with metronomic capecitabine after standard treatment extended DFS among women with operable triple-negative breast cancer, according to study results presented at ASCO20 Virtual Scientific Program.
The regimen appeared safe and well-tolerated, researchers noted.
“Triple-negative breast cancer has the worst outcome among all subtypes of breast cancer,” Xi Wang, MD, of the department of breast oncology at Sun Yat-Sen University Cancer Center in China, said during a presentation. “Effective strategies to reduce risk [for] relapse are a critical clinical need.”
Metronomic chemotherapy has demonstrated antitumor efficacy by inhibiting angiogenesis and stimulating immune responses to reduce tumor metastases, Wang said. Because capecitabine is an orally administered, highly efficacious and well-tolerated chemotherapeutic for metastatic breast cancer, it is potentially an ideal drug for metronomic administration, he added.
Wang and colleagues conducted a phase 3 trial that included 434 women (age range, 18 to 70 years) with operable stage IB to stage IIIC triple-negative breast cancer. All women underwent standard local and systemic treatment with curative intent — consisting of surgery, chemotherapy and radiation therapy, if indicated — and had adequate organ function.
Treatment groups were balanced with regard to age, menopausal status, tumor size and lymph node status.
Researchers randomly assigned 213 women to observation. The other 221 received maintenance therapy with metronomic capecitabine dosed at 650 mg/m² twice daily for 1 year.
DFS served as the primary endpoint. Secondary endpoints included distant DFS, OS and safety.
Median follow-up was 56.5 months.
Researchers reported significantly better 5-year DFS (83% vs. 73%; HR = 0.63; 95% CI, 0.42-0.96) and distant DFS (85% vs. 76%; HR = 0.56; 95% CI, 0.37-0.9) in the capecitabine group. However, the difference in 5-year OS between the capecitabine and observation groups did not reach statistical significance (85% vs. 81%; HR = 0.74; 95% CI, 0.47-1.18).
Subgroup analyses showed similar treatment effects with capecitabine regardless of age, menopausal status, histological grade, pathologic stage, tumor size and lymph node status.
The majority of women (91.4%; n = 202) assigned capecitabine completed 1 year of therapy. Of these women, 44 required one interruption and six required two interruptions. The median relative dose intensity for capecitabine was 84.7%.
The most common capecitabine-related adverse event was hand-foot syndrome (all grade, 46%; grade 3 or higher, 7.7%). All other events were grade 1 or grade 2; these included leukopenia (24%), hyperbilirubinemia (13%), gastrointestinal pain (7%) and elevated serum transaminases (5%).
“The addition of metronomic capecitabine maintenance to standard treatment significantly improved DFS [among] patients with early triple-negative breast cancer,” Wang said. “This is the first phase 3 clinical trial to apply a metronomic chemotherapy in early triple-negative breast cancer ... and obtain positive results. Metronomic capecitabine for 1 year was safe and well-tolerated.”
Reference:
Wang X, et al. Abstract 507. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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Amy Tiersten, MD
This very exciting study shows an impressive DFS benefit in the adjuvant setting for capecitabine among women with early-stage triple-negative breast cancer. We currently only have positive data for capecitabine for patients with residual disease after neoadjuvant therapy, but this study suggests this benefit could extend to all comers. It will be interesting to see if there is an impact on OS with further follow-up.
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Wang X, et al. Abstract 507. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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