Standard Adjuvant Chemotherapy Compared to Capecitabine in Early Breast Cancer

Standard adjuvant chemotherapy continued to show a superior recurrence-free survival (RFS) compared with capecitabine for older patients with early breast cancer, particularly for those with hormone receptor-negative disease, reported a 10-year update of the CALGB 49907 Trial. The findings were recently published in theJournal of Clinical Oncology.

The study had a noninferiority trial design and between September 15, 2001, and December 29, 2006, enrolled 633 women aged 65 years or older who had early breast cancer. Patients were randomized to receive capecitabine alone or a standard adjuvant chemotherapy regimen, which was the physician’s choice of cyclophosphamide, methotrexate, and fluorouracil (CMF) or cyclophosphamide and doxorubicin (AC).

At 10 years of follow-up, patients who received standard adjuvant chemotherapy continued to have a significantly higher RFS rate compared with patients who received capecitabine (56% vs 50%; HR=0.80; P=0.03). The standard adjuvant chemotherapy group also had significantly higher breast cancer–specific survival rates (88% vs 82%; HR=0.62; P=0.03). The overall survival difference between the treatment groups, however, lacked statistical significance (62% vs 56%; HR=0.84; P=0.16).

An unplanned subset analysis revealed that receptor status may influence response to treatment. Specifically, patients with hormone receptor-negative disease had a significantly improved RFS with standard adjuvant chemotherapy compared with capecitabine (HR=0.66; P=0.02), whereas patients with hormone receptor-positive disease did not have such a benefit from standard adjuvant chemotherapy compared with capecitabine (HR=0.89; P=0.43). Patients with triple-negative breast cancer had significantly improved RFS with standard adjuvant chemotherapy compared with capecitabine (HR=0.61; P=0.03).

“Data again failed to show non-inferiority of capecitabine to standard chemotherapy,” Inder Mehmi, MD, medical oncologist at City of Hope in Simi Valley, California, told Cancer Network. He was not involved in the CALGB 49907 trial. “When this data is taken together with other studies that have looked at capecitabine as a single-agent adjuvant chemotherapy for early stage breast cancer in older women, it does not have a role in early stage breast cancer.”

 “Additionally, when hormone-positive breast cancer and triple-negative breast cancer were analyzed, no one group stood out to have equal or better benefit from capecitabine when compared to standard chemotherapy,” Mehmi added.

The long-term follow-up study also showed that at the time of analysis 278 patients (43.9%) had died, and most of the deaths were due to causes other than breast cancer (37.4%) or unknown causes (32.0%).

A total of 85 patients died (30.6%) from breast cancer itself, and a lower proportion of patients died from breast cancer in the standard adjuvant chemotherapy group compared with the capecitabine group (10% vs 16%; P=0.045). In addition, 16.9% of the standard adjuvant chemotherapy group and 12.4% of the capecitabine group developed second new cancers.

Mehmi cautioned that CMF and AC are not the most common regimens used in the adjuvant setting. Most often, he said, a taxane, such as docetaxel or paclitaxel, is combined with cyclophosphamide as doxorubicin-free chemotherapy or in combination with cyclophosphamide and doxorubicin.

“There is little to no data available comparing capecitabine to either the docetaxel/cyclophosphamide or doxorubicin/cyclophosphamide/paclitaxel regimen,” he said.  

Mehmi explained that the study data, however, “yet again” prove that when patients are given chemotherapy in early stage breast cancer, it leads to better survival since the cause of death for most of these patients were of non-breast cancer reasons.