Elderly patients with early-stage breast cancer derived no survival benefit from capecitabine monotherapy

SAN ANTONIO — Capecitabine monotherapy did not improve outcomes in elderly patients with moderate- to high-risk early-stage breast cancer, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

Standard chemotherapy is too toxic for this patient population. Capecitabine, however, is associated with fewer side effects than standard chemotherapy agents.

In the ICE trial, Gunter von Minckwitz, MD, chairman of the German Breast Group and professor of gynecology at University of Frankfurt in Germany, and colleagues evaluated capecitabine as single-agent chemotherapy in women aged ≥65 years who also took ibandronate, a bisphosphonate.

Gunter von Minckwitz

Researchers randomly assigned 677 patients to receive ibandronate in one of two doses based on patient preference — 50 mg orally daily, or 6 mg intravenously every 4 weeks — for 2 years, plus capecitabine 2,000 mg/m² orally daily on days 1-14 every 3 weeks for six cycles. The other 681 patients received ibandronate alone. Two-thirds of patients opted for the oral ibandronate regimen, and median time on ibandronate treatment was comparable between those on the oral and IV regimens.

DFS served as the primary endpoint. OS, compliance and safety served as secondary endpoints.

Median patient age was 71 years in both treatment arms, and about 25% of patients in each group were aged ≥75 years. About 80% of patients in both groups had hormone receptor-positive disease and had received endocrine therapy.

Other patient and tumor characteristics — including Charlson co-morbidity index, co-medications, tumor grade, HER-2 status, triple-negative disease and receipt of aromatase inhibitors — were balanced between cohorts.

Median follow-up was 61 months.

Despite the use of ibandronate, researchers still observed frequent bone-related events — such as fractures, surgery and new osteoporosis — in both arms.

Incidence of bone-related events was 25% among those who received capecitabine and 24.7% among those who did not (OR=1.06; 95% CI, 0.82-1.37). Among patients with hormone-receptor positive disease, incidence was higher in those treated with aromatase inhibitors (OR=1.71; 95% CI, 0.89-3.28) compared with those treated with tamoxifen.

Researchers observed no significant difference in 3-year DFS (85.4% vs. 84.3%) or 5-year DFS (78.8% vs. 75%) between those who received capecitabine and those who did not, translating to an HR of 1.04 (95% CI, 0.84-1.29).

Rates of OS at 3 years (95% vs. 94%) and 5 years (90% vs. 88%) also were comparable between those who received capecitabine and those who did not.

“At the time of analysis, these patients had a median age of almost 77 years,” von Minckwitz said during a press conference. “The very favorable survival at 5 years shows that these patients have a sufficient life expectancy and that they should be treated sufficiently according to the best options available.”

The rate of grade 3 or grade 4 adverse events was higher among patients who received capecitabine (31% vs. 8.7%). Eight percent of patients assigned capecitabine discontinued treatment due to adverse events, and 8% discontinued for other reasons.

“These patients have to be followed further,” von Minckwitz said. “As we know from other capecitabine studies, long-term follow-up after adjuvant therapy often is necessary to see real differences.”

For more information:

von Minckwitz G. Abstract #S3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.

Disclosure: The researchers report research funding from AstraZeneca and Roche.