Phase II open-label study of sunitinib in patients with advanced breast cancer.

This multicenter, open-label phase II study was conducted to evaluate sunitinib monotherapy in patients with either metastatic or locoregionally recurrent advanced breast cancer. Patients received sunitinib 37.5 mg on a continuous daily dosing schedule. The primary endpoint was objective response rate (ORR); the predefined target ORR was 25 %. All 83 patients enrolled into the study received study treatment. The majority of patients (90 %) had metastatic disease; 92 % had received prior systemic therapies, and 60 % had received two or more regimens for early and/or advanced disease. The ORR was 8 % (95 % exact CI, 4-17), comprising seven partial responses. In patients with superficial lesions (defined as cutaneous or palpable chest wall lesions), the ORR was 20 % (three of 15 evaluable patients), which was higher than that in patients with non-superficial disease (9 %; six of 64 patients). Median progression-free survival in the overall population was 3.6 months (95 % CI, 2.4-3.9); median overall survival was 15.6 months (95 % CI, 14.0-22.7). No new or unexpected safety findings were reported. The most commonly reported adverse events (AEs) were fatigue (60 %), diarrhea (54 %), and nausea (49 %). The most commonly reported grade 3/4 AEs were fatigue (17 %), neutropenia (16 %), and thrombocytopenia (11 %). Four patients (5 %) had a dose reduction due to an AE, and 39 patients (47 %) had temporary discontinuations of therapy due to AEs. Two on-study deaths were reported, one due to a pulmonary embolism (considered related to treatment) and one attributed to dyspnea and a myocardial infarction (considered unrelated to treatment). Patient-reported outcomes suggested that sunitinib treatment did not have a negative impact overall on patients' functional domains or the majority of symptom scales. The trial did not meet its prespecified primary endpoint, and in view of the negative results obtained in several other trials, sunitinib will not be developed further for this indication.