SAN ANTONIO — Single-agent treatment with the chemotherapy drug capecitabine is no better than forgoing cytotoxic treatment altogether for elderly patients with moderate- to high-risk early-stage breast cancer, according to results from the phase 3 ICE trial, the largest breast cancer trial to date in elderly patients.
Capecitabine monotherapy, which is taken orally, is frequently used in elderly patients who cannot tolerate the harsh toxic effects of conventional combination anthracycline and taxane therapies, said the study's lead investigator, Gunter von Minckwitz, MD, professor of gynecology at University of Frankfurt in Germany, and chair of the German Breast Group.
But the findings, which he presented here at the San Antonio Breast Cancer Symposium 2014, no longer support this practice. "Combination therapy is strongly supported, even in patients with a higher age at diagnosis," he said.
ICE, a prospective, multicenter, randomized trial, involved patients with node-positive or high-risk node-negative disease. Mean age was 71 years, and all patients received ibandronate for 2 years. About half the 1358 patients were randomized to receive six cycles of capecitabine; the other half received no cytotoxic therapy.
All patients were considered inappropriate candidates for conventional combination anthracycline and taxane chemotherapy, Dr von Minckwitz explained.
"One-quarter of these patients were older than 75 years, 10% were somewhat frail (with a Charlson comorbidity index of 2), and 15% to 17% of patients showed some reduced physical function and disabilities," he reported.
For the primary end point of the study, which was invasive disease-free survival, there was no significant difference between patients who were treated with capecitabine and those who were not at 3 years (85.4% vs 84.3%) or 5 years (78.8% vs 75.0%).
There were more grade 3 and 4 adverse events in patients who recevied capecitabine, but "nothing unexpected," he explained.
Although the study results clearly show that capecitabine monotherapy is not beneficial in the elderly breast cancer population, they open the question of how best to treat these patients.
For Dr von Minckwitz, the answer is to treat more aggressively.
The results, when considered with findings from the CALGB 49907 study (N Engl J Med. 2009;360:2055-2065), which compared capecitabine monotherapy with standard combination therapy (cyclophosphamide, methotrexate, plus fluorouracil [CMF] or doxorubicin plus cyclophosphamide [AC]), support the use of combination therapy even in older women.
Because these patients have a reasonable life expectancy, "they should be treated sufficiently and according to the best options regarding their breast cancer," Dr von Minckwitz said during a press conference. "A patient has to be really unfit before I would not give her the chemotherapy."
But for other clinicians, the toxicity of combination therapy, compared with capecitabine monotherapy, which was observed in the CALGB 49907 study (64% vs 33%), might be too great a risk to take.
Study investigator Sibylle Loibl, MD, who is cochair of the German Breast Group, expressed this reservation and said that "maybe ibandronate in the elderly might be enough."
Although the CALGB 49907 trial clearly showed that combination AC or CMF therapy was superior to capecitabine in older women, "there was always the question of whether capecitabine was better than nothing," said Ann Partridge, MD, associate professor at Harvard Medical School and oncologist at the Dana-Farber Cancer Institute in Boston, who was one of the CALGB 49907 investigators.
"Now we know that it is not, and only adds toxicity," she told Medscape Medical News. "Unfortunately, for older patients who are at risk of recurrence after early-stage breast cancer, capecitabine does not provide any clear risk reduction," Dr Partridge added.
The study was funded by Roche and AstraZeneca. Dr von Minckwitz's institution received research funding and medication for this study. The authors have disclosed no relevant financial relationships.
San Antonio Breast Cancer Symposium (SABCS) 2014: Abstract S3-04. Presented December 11, 2014.
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Cite this: Capecitabine No Benefit in Elderly Breast Cancer Patients - Medscape - Dec 12, 2014.