A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the Princess Margaret Hospital, The University of Chicago, and California Cancer Phase II Consortia.

Abstract

5038 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Thirty four eligible pts with recurrent or metastatic EC who had received up to 1 prior chemotherapy (CT) regimen for metastatic disease have been treated with sunitinib is 50 mg daily (OD) for 4 consecutive weeks followed by 2 weeks off. Dose could be reduced to 37.5 mg qd and then 25 mg qd in the setting of toxicity. Imaging was repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). Secondary objectives are time to progression (TTP), overall survival (OS) and safety. Results: Study is on hold having completed accrual. Of the 34 patients accrued and treated, data is currently available for 30 of the pts (median age: 66 range: 41-83). ECOG PS was 0 (10 pts), 1 (18 pts), or 2 (2 pt). Histology was endometrioid (21 pts), serous (6), carcinosarcoma (3). Most pts had high-grade histology (G3:15; G2:4; G1:5; NA:6).19 pts had prior adjuvant CT; of them, 12 pts had 1 prior CT for advanced EC and 9 pts had prior radiotherapy. 77 cycles of sunitinib (median; 2 range: 1-14) have been administered. Of the 20 patients evaluable for response (5 patients inevaluable, 9 patients pending information), partial response was achieved by 3 pts (ORR = 15%), and 5 other pts had a best response of stable disease; 4 of these pts remained progression-free ≥ 6 months. Median TTP = 2.53 months (95% CI:2.47-NR) and median OS = 19 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in > 10% of pts were fatigue (12 pts, 40%) and hypertension (6 pts, 20%). At least 1 dose reduction was required for 18 of 30 pts (60%). Two pts were inevaluable after receiving < 2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib has demonstrated activity in endometrial cancer and warrants further study No significant financial relationships to disclose.