Gunter von Minckwitz, MD
Older patients with moderate- or high-risk breast cancer had a similar disease-free survival with the bisphosphonate therapy ibandronate alone or in combination with capecitabine, according to a study reported at the 2014 San Antonio Breast Cancer Symposium.
Invasive disease-free survival at 3 years was 85.4% with capecitabine and 84.3% without. A slight advantage in favor of the capecitabine arm had emerged at the 5-year follow-up, but the difference did not achieve statistical significance.
Bone-related events occurred frequently in both treatment groups, supporting the need to consider bisphosphonates for older breast cancer patients, said Gunter von Minckwitz, MD, chair of the German Breast Group (GBG) in Neu-Isenberg.
"The study failed to show that adjuvant capecitabine improves invasive disease-free survival in patients receiving ibandronate," von Minckwitz said at a press briefing December 11. "The outcome of older patients with moderate or high-risk early breast cancer receiving ibandronate alone is very favorable."
"Due to the excellent overall prognosis and the high proportion of luminal type tumors, longer follow-up to observe potential late effects of capecitabine is required."
Despite the lack of difference between treatment groups, von Minckwitz added, the findings support those of the Cancer and Leukemia Group B 49907 trial that demonstrated the benefits of combination chemotherapy in older patients with early breast cancer (N Engl J Med
The findings came from the Ibandronate with or without Capecitabine for Elderly Patients with Early Breast Cancer (ICE) trial, conducted jointly by the GBG and the Breast International Group. The trial evolved from recognition that older patients are underrepresented in clinical trials of breast cancer, despite constituting a majority of breast cancer cases, von Minckwitz said.
The primary objective of the trial was to determine whether the addition of capecitabine to ibandronate would improve outcomes of older patients with intermediate- or high-risk early breast cancer who are unsuitable for standard chemotherapy regimens.
Investigators enrolled patients aged 65 and older with node-positive breast cancer, node-negative tumors 2 cm or larger, grade 2 or 3, or hormone receptor-negative breast cancer and a Charlson comorbidity score of 2 or less.
In total, 1358 patients were randomized to capecitabine 2000 mg/m2
on days 1-14 of 3-week cycles (maximum of 6 cycles) plus ibandronate 50 mg PO daily or 6 mg intravenous every 4 weeks, continued for 2 years or to ibandronate alone. The primary endpoint was disease-free survival.
The median age of patients was 71.About 80% of patients had hormone receptor-positive breast cancer, and about 70% had received only aromatase inhibitors. Von Minckwitz noted that 65.4% of patients received oral ibandronate and 34.6% received the intravenous formulation. Subsequently, 2.4% and 3.6% of patients in each group switched ibandronate formulations, respectively.
The 5-year invasive disease-free survival was 78.8% with capecitabine and 75.0% with ibandroante alone (P
= 0.7012). Subgroup analysis failed to identify a consistent treatment benefit.
Bone-related events included fractures, surgery, or new osteoporosis but not bone metastasis. The incidence of bone events was 25.0% in the capecitabine arm and 24.7% with ibandronate alone.
During the discussion that followed the presentation, von Minckwitz said treatment for older patients with intermediate- or high-risk early breast cancer should be individualized according to patient characteristics, including comorbidity burden. Whether a patient would receive bisphosphonate monotherapy would depend on demographic and clinical factors.
Adherence to bisphosphonates is an issue with older breast cancer patients, he said. It is of greater concern, however, that evidence shows a large proportion of older breast cancer patients receive no systemic therapy or receive inadequate therapy.
von Minckwitz G, Reimer T, Potenberg J, et al. The phase III ICE study: Adjuvant Ibandronate with or without capecitabine in elderly patients with moderate or high risk early breast cancer. Presented at: 2014 San Antonio Breast Cancer Symposium December 9-12, 2014, San Antonio, TX. Abstract S3-0
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