Capecitabine plus docetaxel, along with Herceptin for women whose tumors are HER2-positive, may be an active and well-tolerated neadjuvant option for women with invasive breast cancer, according to a presentation at the U.S. Breast Cancer Symposium.

The Phase II XeNA (Xeloda in NeoAdjuvant), open-label trial is designed to investigate the activity of a short non-anthracycline-based preoperative treatment for early breast cancer in both HER2-negative and HER2-positive patients. Interim data analysis shows that promising results were achieved after only four cycles of pre-surgical treatment compared with the standard eight cycles.

The majority of the 156 patients responded to therapy regardless of HER2 status, and both patient groups experienced a clinically significant reduction in tumor size.

"These early XeNA trial results highlight the potential of the Xeloda/Taxotere combination, with Herceptin for HER2-positive patients, to provide an effective and safe treatment option in a shorter period of time before surgery among patients with invasive breast cancer," said Debu Tripathy, MD, lead investigator of the XeNA trial and Professor of Medicine and Director of the Komen/UT Southwestern Breast Cancer Research Program at the University of Texas Southwestern Medical Center at Dallas.

"While these findings warrant additional studies, the real-world impact of the reduction in tumor size could translate into the difference between a lumpectomy instead of a more drastic mastectomy."

In the interim analysis, following four treatment cycles, the combination of capecitabine, docetaxel and Herceptin in HER2-positive patients resulted in a 73 percent clinical response rate (complete and partial response) and a 50 percent pathologic response (pathologic complete response, the absence of histological evidence of cancer cells in the tissue specimen, plus near pathological complete response, which is less than or equal to 5 millimeters of residual cancer).

Additionally, HER2-negative patients experienced a clinical response rate of 76 percent and 15 percent pathological response with the two-agent combination. In patients with HER2-negative tumors, a decrease from 6.1 to 2.8 centimeters was observed; in HER2-positive patients, the reduction was from 5.6 to 1.6 centimeters.
The trial enrolled 157 (156 evaluable) patients with newly diagnosed invasive breast cancer (planned sample size 122 HER2-negative; 34 HER2-positive).

Efficacy results for 134 patients, as well as toxicity data for the total evaluable population of 156 patients, were included in this interim analysis.

The primary endpoint was the rate of pathological complete response rate plus near complete pathologic response rate in the affected breast after preoperative administration two-agent therapy for HER2-negative patients and in combination with Herceptin for HER2-positive patients.

Secondary endpoints included safety profile; quality of life; local recurrence; disease-free survival; distant disease-free survival; and overall survival. Other secondary endpoints included complete pathologic response in sentinel and axillary, or underarm, lymph nodes; clinical response rate; ability of blood and tissue markers; genomic profiling of the tumors; circulating tumor cells for HER2-positive patients; and p53 gene mutations to predict short-term clinical and pathological responses.

Participation was limited to patients with no evidence of metastatic disease except ipsilateral axillary lymph nodes and no prior history of treatment.

Patients received four three-week cycles of the treatment regimen. HER2-negative patients received capecitabine 825 mg/m² twice a day for 14 days with seven days off, and also received docetaxel 75 mg/m² intravenously on the first day. HER2-positive patients were on the same regimen, but also received Herceptin each week with a loading dose of 4 mg/kg for 90 minutes followed by 2 mg/kg for 30 minutes for a total of 12 weeks before definitive surgery.

The most frequent adverse events were hematologic toxicities and hand-foot syndrome. Five HER2-negative patients and one HER2-positive patient experienced progression before surgery. There were no treatment- related deaths prior to surgery, nor were there clinical or subclinical cardiac events.