No Survival Benefit With Adjuvant Capecitabine in Early-Stage TNBC

Gina Columbus @ginacolumbusonc
Published: Wednesday, Dec 05, 2018

Miguel Martin, MD, PhD

Miguel Martin, MD, PhD

Adjuvant treatment with capecitabine in patients with early-stage triple-negative breast cancer (TNBC) did not significantly improve disease-free (DFS) or overall survival (OS) compared with observation, according to results from the phase III GEICAM/CIBOMA trial that were presented at the 2018 San Antonio Breast Cancer Symposium.1

“We were disappointed to find that adding adjuvant capecitabine to the standard treatment did not significantly improve disease-free or overall survival,” said lead study author Miguel Martín, MD, PhD, professor of medicine and head of the Medical Oncology Service at Hospital Gregorio Marañón, Universidad Complutense, Madrid, Spain.

Additionally, data from a subset analysis showed that patients with nonbasal-like TNBC who received capecitabine had a 49% reduction in the risk of disease progression and a 52% reduction in the risk of death versus those with nonbasal-like disease on the observation arm.

“However, given that we found a subset of the patients with nonbasal-like disease 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 breast cancer patients with residual disease after neoadjuvant chemotherapy, we strongly recommend that patients with triple-negative breast cancer discuss adjuvant capecitabine with their oncologists.”

Findings from the CREATE-X trial previously showed that the addition of adjuvant capecitabine following standard neoadjuvant chemotherapy containing anthracycline, taxane, or both was safe and effective in prolonging DFS and OS among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing.2

“Patients with early-stage triple-negative breast cancer are usually treated with surgery and chemotherapy, and sometimes radiotherapy,” concluded Martín. “New therapeutic approaches are urgently needed, however, because the risk of relapse is high: 7% to 10% of those with stage I disease relapse, 15% to 20% of those with stage II disease, and 25% to 50% of those with stage III disease.”

In the randomized, phase III GEICAM/CIBOMA trial, 876 patients with early-stage TNBC that was estrogen receptor–, progesterone receptor–, and HER2-negative who underwent surgery and chemotherapy were randomized 1:1 to receive 8 cycles of oral capecitabine at 1000 mg/m2 twice daily for 14 days every 3 weeks (n = 448) or observation (n = 428).

Patients had stage T1c-3, N0-N3a, or M0 disease. To be eligible for enrollment, patients also had to have received standard neoadjuvant and adjuvant chemotherapy with anthracycline with or without taxanes, and underwent surgery with negative margins. Six cycles of chemotherapy were mandatory except for patients with N0 tumors.

Patients were stratified by institution, basal phenotype according to CK5/6 and/or EGFR staining, number of axillary lymph nodes (0 vs 1-3 vs ≥4), and prior chemotherapy with anthracycline versus anthracycline plus taxanes. The primary endpoint was DFS and OS, subgroup analyses, safety, and biomarkers.

The median age was 49.5 years, with 60.7% of patients from Spain and 39.3% from Latin America. Most patients were postmenopausal (68.4%) compared with premenopausal (31.5%). The majority of patients were stage II in both arms (60.3% with capecitabine vs 63.3% with observation). In the capecitabine arm, 54.5% of patients had node-negative tumors, 27% with 1 to 3 positive nodes, 17.2% with ≥4 positive nodes, and 1.3% had unavailable status. Among those on the observation arm, 56.5% had node-negative status, 29.0% had 1 to 3 positive nodes, 14.3% had ≥4 positive nodes, and 0.2% had unavailable node status.

Adjuvant chemotherapy alone was given in 78.8% of those on the capecitabine arm and 82.2% on observation, while neoadjuvant and adjuvant chemotherapy was given in 19.9% and 17.5% in capecitabine and observation, respectively. These data were unavailable for 1.3% and 0.2% of the capecitabine and observation groups, respectively.

Pathologic complete response (pCR) to neoadjuvant chemotherapy among arms was comparable (24.7% on capecitabine vs 25.3% on observation).

At a median follow-up of 7.3 years, results showed that the 5-year DFS rates were 79.6% and 76.8% in the capecitabine and observation arms, respectively, which was not deemed statistically significant (P = .135). There were 105 events in the capecitabine arm and 120 in the observation arm (HR, 0.82; 95% CI, 0.63-1.06; P = .135). The adjusted hazard ratio for stratification variables was 0.79 (95% CI, 0.61-1.03; P = .082).

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