A phase II trial of sunitinib in women with metastatic or recurrent endometrial carcinoma: a study of the Princess Margaret, Chicago and California Consortia.

OBJECTIVE: Treatment options remain limited for women with relapsed/metastatic endometrial cancer (EC). Angiogenesis is one of the major components of tumor progression and thus an attractive target. The aim of this phase II trial was to assess the efficacy and tolerability of sunitinib, an oral multitargeted receptor tyrosine-kinase inhibitor with antiangiogenic and antitumor activity in the treatment of recurrent EC.
METHODS: We performed a multicenter, single arm, two-stage phase II study of sunitinib, 50mg daily administered on a 4 weeks on-2 weeks off schedule. Eligibility criteria included recurrent/metastatic EC or carcinosarcoma with no more than one prior line of chemotherapy. The primary endpoint was objective response rate.
RESULTS: 34 women were enrolled; 33 received at least one dose of sunitinib and were included in the analyses. Six women (18.1%) had a partial response and six additional women (18.1%) stable disease. In total, ten patients (30.3%) had disease control for at least 6 months and of these, seven were controlled for more than one year. Median progression free and overall survival times were 3 months and 19.4 months, respectively. Adverse events related to treatment were frequent. At least one grade 3 toxicity occurred in 30 patients and dose reductions were required in 17 patients (52%). The most common grade 3 toxicities were fatigue, hypertension, palmar-plantar erythrodysesthesia, diarrhea and hematologic.
CONCLUSION: Sunitinib therapy showed promising activity in women with recurrent EC. Toxicity was seen frequently but was manageable. Anti-angiogenic agents warrant further investigation in EC to define which patients will derive the greatest benefit.