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.

Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer.

This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m(2) (1,000 mg/m(2) in patients >65 years) BID on days 1-14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16-1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.