Abstract P6-12-02: A Randomized Phase II Study of Sunitinib vs. Standard of Care for Patients with Previously Treated Advanced Triple-Negative Breast Cancer

Background Triple-negative (TN) breast cancer (BC), which comprises approximately 15% of all BC cases, has a particularly poor prognosis. In a phase II study in patients with heavily pretreated metastatic BC, 15% of patients (3/20) with TN disease achieved PRs following treatment with the multitargeted tyrosine kinase inhibitor sunitinib. A randomized, open-label phase II study was conducted to compare the PFS obtained with sunitinib monotherapy and single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced TNBC, results of which are reported here. MethodsEligible patients (≥18 years, ECOG PS 0-2) with advanced ER/PR/HER2- negative BC had been treated with an anthracycline and a taxane in the adjuvant or advanced setting; if disease-free >6 months post-adjuvant therapy, patients should have received 1-2 prior chemotherapy regimens for advanced BC. Patients were randomized (1:1) to receive either sunitinib 37.5 mg po daily or the investigator9s choice of SOC therapy (capecitabine: 2,000-2,500 mg/m2 po days 1-14 q3w; vinorelbine: 25-30 mg/m2 IV or 60-80 mg/m2 po qw; docetaxel: 75-100 mg/m2 IV q3w; paclitaxel: 175-200 mg/m2 IV q3w or 80-90 mg/m2 IV qw or qw3/4; or gemcitabine: 800-1,250 mg/m2 IV qw2/3). Patients with documented disease progression per RECIST in the SOC arm were offered sunitinib therapy. The primary endpoint was PFS as assessed by independent central review; secondary endpoints included RECIST-defined ORR, OS, and safety. Log-rank tests were used to compare treatment arms for time-to-event endpoints. Results At data cut-off (April 1, 2010), the ITT population comprised 217 female patients (sunitinib: 113; SOC: 104). Based on independent central review, median PFS was 2.0 months in the sunitinib arm and 2.7 months in the SOC arm (HR: 1.20; 95% CI: 0.89-1.63; 1-sided P=0.889). Likewise, sunitinib did not prolong median OS, which was 9.4 months in the sunitinib arm and 10.5 months in the SOC arm (HR: 1.22; 95% CI: 0.89-1.68; 1-sided P=0.892). The ORR was 3% with sunitinib and 7% with SOC (odds ratio: 0.37; 95% CI: 0.06-1.70; 1-sided P=0.963). The most frequent grade 3/4 AEs of any cause were neutropenia (21%), thrombocytopenia (11%), asthenia (10%), and leucopenia (10%) in the sunitinib arm and neutropenia (11%), fatigue (5%), and hand-foot syndrome (5%) in the SOC arm. Treatment was discontinued due to AEs in 35% and 6% of patients in the sunitinib and SOC arms, respectively. Conclusions The study did not meet its primary or secondary endpoints, as sunitinib did not improve PFS, OS, or ORR compared with SOC therapy. Based on these results, sunitinib monotherapy is not recommended for treatment of patients with previously treated advanced TNBC. There remains an urgent need for effective treatments for patients with TNBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-12-02.