Addition of Sunitinib to Capecitabine Does Not Improve Outcome in Previously Treated Metastatic Breast Cancer
A trial reported in Journal of Clinical Oncology by John P. Crown, MD, of the Irish Cooperative Oncology Research Group, and colleagues assessed the addition of the antiangiogenesis agent sunitinib (Sutent) to capecitabine (Xeloda) in patients with previously treated metastatic breast cancer who had received taxane and anthracycline therapy. The addition of sunitinib did not improve progression-free survival, overall survival, or response rate.
Study Details
In this trial, 442 patients with metastatic breast cancer from 105 centers in 18 countries were randomly assigned to receive either sunitinib 37.5 mg/d plus capecitabine 2,000 mg/m2 on days 1 to 14 every 21 days (n = 221) or capecitabine 2,500 mg/m2 alone (n = 221 each). Eligibility criteria included prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary endpoint was progression-free survival.
The combination and monotherapy groups were well balanced for age (median, 52 and 54 years), ECOG performance status (0 or 1 in 99% of both), number of metastatic sites (> 2 in 50% of both), histology (ductal in 82% and 80%), receptor status (estrogen receptor–positive in 66% and 68%, progesterone receptor–positive in 50% and 54%, HER2-positive in 13% and 11%, and triple-negative in 27% of both), number of prior chemotherapy regimens (> 1 in 55% of both ), and prior chemotherapy (neoadjuvant/adjuvant only in 23% and 21%, one for advanced breast cancer in 63% and 62%).
No Difference in Progression-Free Survival
Median follow-up was 14.3 months. A total of 35% of patients in the monotherapy group crossed over to sunitinib after progression. Progression-free survival based on independent radiologic review did not differ significantly between the combination and monotherapy groups (median, 5.5 vs 5.9 months, hazard ratio [HR] = 1.22, P = .941). There were no significant differences between groups in overall survival (median, 16.4 vs 16.5 months, HR = 0.99, P = .484), objective response rate in patients with measurable disease (19% vs 18%), or median duration of response (9.0 vs 8.8 months). Although a previous phase II trial indicated that sunitinib has activity in triple-negative disease, the addition of sunitinib did not improve progression-free survival in this subgroup of patients in the current trial.
Hematologic adverse events were more common and more severe in the combination group, including grade 3 or 4 neutropenia in 31% vs 17% and thrombocytopenia in 4% vs 0%. Nonhematologic adverse events were also more common and more frequently of higher grade in the combination arm, with the exception of hand-foot syndrome.
The authors noted that the optimal dosing and sequencing of sunitinib with cytotoxic agents have yet to be determined, and that this factor may have affected the results of the trial. They concluded: “[T]he combination of sunitinib and capecitabine failed to improve [progression-free survival] compared with capecitabine alone when administered to patients with [metastatic breast cancer] who had received prior therapy with anthracyclines and taxanes and exhibited an unfavorable toxicity profile. The sunitinib plus capecitabine regimen evaluated in this study is not recommended for treatment of this patient population.”
The trial was supported by Pfizer.
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