NEW YORK (Reuters Health) – In a phase III, multinational study of patients with heavily pretreated metastatic breast cancer, adding sunitinib to capecitabine provided no benefit, and in fact just worsened side effects.
“Moving forward,” the investigators comment in their report, “it is apparent that defining the optimal biologic dose of antiangiogenic agents alone and in combination with chemotherapy is a critical need in oncology drug development.”
Dr. Gilles Romieu, at the Institut régional du Cancer de Montpellier, France, and colleagues explain that sunitinib inhibits tumor neoangiogenesis and has an established role in treating metastatic renal cancer and other cancers.
On the basis of favorable preclinical and clinical findings, the team conducted an open-label, randomized trial of capecitabine with or without sunitinib in 442 patients with metastatic breast cancer after prior therapy with anthracyclines and taxanes.
Specifically, “In the combination arm, patients received capecitabine orally at a starting dose of 2,000 mg/m² (1,000 mg/m² twice daily) on days 1 to 14 of a 3-week cycle plus sunitinib orally at a starting dose of 37.5 mg once daily. In the monotherapy arm, patients received capecitabine at a starting dose of 2,500 mg/m² (1,250 mg/m² twice daily) on days 1 to 14 of a 3-week cycle.”
Median follow-up was 14.3 months. Median progression-free survival, the primary end point, was not significantly different in the two arms: 5.5 months with combination treatment, versus 5.9 months with monotherapy (p=0.941).
Similarly, the authors report in the Journal of Clinical Oncology online July 15, overall survival “was virtually identical in the two treatment arms, with medians of 16.4 and 16.5 months.”
Hematologic adverse events were more severe and more frequent with capecitabine plus sunitinib than with capecitabine alone, according to the report. For example, rates of grade 3 or 4 neutropenia were 31% and 4% in the two arms, respectively, and corresponding rates of thrombocytopenia were 17% and 0%.
Nonhematologic adverse events were also worse with combination treatment, except for hand-foot syndrome.
The authors note that despite a promising phase II trial with sunitinib and the success of bevacizumab with chemotherapy in metastatic breast cancer, four phase III trials with sunitinib have now had disappointing results.
Given their findings, Dr. Romieu and colleagues conclude, “The sunitinib plus capecitabine regimen evaluated in this study is not recommended for treatment of this patient population.”
SOURCE: Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer
J Clin Oncol 2013;31.
