Capecitabine Further Improved Outcomes of Residual Breast Cancer After Neoadjuvant Therapy

Masakazu Toi, MD, PhD

Patients with breast cancer who still had residual disease after undergoing neoadjuvant chemotherapy and surgery had improved survival outcomes with the addition of adjuvant capecitabine to standard treatment.

This conclusion comes from the phase III CREATE-X trial presented by Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, at the 2015 San Antonio Breast Cancer Symposium (SABCS).

“After standard neoadjuvant chemotherapy containing anthracyclines and/or taxanes, postoperative adjuvant use of capecitabine improved disease-free survival significantly in HER2-negative primary breast cancer patients with pathologically proven residual invasive disease,” Toi said during a press conference. “The balance of benefit and toxicity would favor the use of capecitabine in the post-neoadjuvant chemotherapy situation, but prediction for the therapeutic benefit needs to be investigated further.”

According to Toi, patients with residual disease after neoadjuvant chemotherapy are more likely to have disease relapse and little is known about whether postoperative systemic chemotherapy has any positive effect on survival.

The CREATE-X trial was designed to test whether capecitabine improved disease-free survival for patients with residual disease. The trial included 910 patients with HER2-negative invasive breast cancer who had residual disease after undergoing treatment with an anthracycline and/or taxane-based neoadjuvant chemotherapy. Patients were randomly assigned to radiation therapy and hormone therapy (standard treatment) with or without 1,250 mg/m² capecitabine twice daily (n = 455). Capecitabine was given on days 1 to 14 every 3 weeks for eight cycles. Patients who were hormone-receptor positive received hormone therapy.

In 2015, a pre-planned interim analysis was conducted and the Independent Data Monitoring Committee recommended discontinuation of the trial based on the study protocol.

Patients assigned to the capecitabine arm had significant improvements in both 2-year (87.2% vs 80.4%) and 5-year disease-free survival (74.1% vs 67.7%; hazard ratio [HR], 0.70 [95% confidence interval, 0.53–0.93]).

“Overall survival was significantly improved by capecitabine adjuvant therapy for non-pCR or node-positive patients after neoadjuvant chemotherapy,” Toi said.

Updated analyses of the data showed that the 2-year median overall survival was 96.4% with capecitabine compared with 94.2% for those in the control arm.

Toi also noted that the researchers are conducting subset analyses to determine whether certain groups of patients benefited more than others from capecitabine. For example, they are looking at whether hormone-receptor status affected outcomes, he said.