Phase III Randomized Trial of Sunitinib (SU) vs. Capecitabine (C) in Patients (Pts) with Previously Treated HER2-Negative Advanced Breast Cancer (ABC).

Abstract

Abstract BackgroundC monotherapy is approved for pts with ABC who progress after anthracycline (A) and taxane (T) therapies. SU is an oral, multitargeted tyrosine kinase inhibitor that has demonstrated a single-agent response rate of 11% in heavily pretreated ABC.MethodsTo test the hypothesis that SU is superior to C, we compared the 2 agents in a multicenter, randomized, open-label, phase III trial of 700 pts. Eligible pts (≥18 yrs, ECOG PS ≤2) had HER2-negative ABC that recurred after A and T therapy in the (neo)adjuvant, metastatic, or locally advanced disease settings. Pts were randomized (1:1) to continuous daily dosing of SU 37.5 mg or to C 1,250 mg/m2 (1,000 mg/m2 in pts >65 yrs) twice daily on days 1–14 q3wk. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR), patient-reported outcomes, and safety.ResultsAfter a pre-planned interim analysis showed that the primary endpoint would not be reached, the Independent Data Monitoring Committee recommended stopping trial enrollment for futility. Pts randomized to SU were offered alternative treatment (tx). As of March 2009, 464 pts were randomized to SU (n=231; mean age 52.7 yrs; 29 pts ≥65 yrs) or C (n=233; mean age 52.4 yrs; 44 pts ≥65 yrs). 22.9% vs. 35.6% of pts continued to receive SU and C, respectively. Tx was discontinued due to adverse events (AEs) in 10.8% of pts in the SU arm vs. 7.7% of pts in the C arm. Most common AEs leading to discontinuation of SU were neutropenia (3 pts) and hand–foot syndrome, congestive cardiac failure, epistaxis, and thrombocytopenia (2 pts each). C was discontinued due to neutropenia in 3 pts. Median PFS was 2.8 mos (95% CI: 2.4–3.9; 162 PFS events) vs. 4.2 mos (95% CI: 3.4–5.0; 135 PFS events) for SU vs. C, respectively (HR 1.473; 95% CI: 1.167–1.858; P<0.001). ORR for SU was 9.1% (95% CI: 5.7–13.6) vs. 12.9% (95% CI: 8.9–17.9) for C. CBR was 14.3% (95% CI: 10.0–19.5) for SU vs. 21.9% (95% CI: 16.8–27.8) for C. Other secondary endpoint analyses are ongoing.ConclusionsAlthough some pts continue to benefit from SU, these data suggest that SU is not superior to C given as monotherapy. The observed AE profiles were similar to those previously reported for SU and C. C was better tolerated than SU. SU cannot be recommended as monotherapy on this dosing schedule. Phase III studies with SU in combination with chemotherapy and other agents are ongoing in ABC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 46.