Open Label, Phase Ii Study Of Axitinib, A Selective Inhibitor Of Vascular Endothelial Growth Factor Receptors, In Patients With Stage Iii Malignant Melanoma.

e22062 Background: This open-label, phase II study investigated the clinical activity and safety profile of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR) in patients with stage III melanoma. Methods: Eligible patients had histology proven stage III melanoma, at least 1 target lesion as defined by RECIST, and no prior systemic therapy. Primary end point was objective response rate (ORR) according to RECIST v1.1; response was also considered if there was a ≥ 25% reduction in the involved nodal basin specific uptake value (SUV) on PET/CT. Secondary endpoints included duration of response (DOR), progression free survival (PFS), and overall survival (OS). Axitinib 5mg was given orally twice each day; treatment continued until tumor progression, unmanageable toxicity, or if the patient withdrew consent. After two months of therapy, patients then underwent definitive surgical resection of their involved nodal basins; one month after surgery patients would restart axitinib. In the 1st stage, 18 patients were to be enrolled; if there was ≥ 1 response, then the study would proceed to the 2nd stage with enrollment of additional 14 patients. At the end of the study, if there were at least 4 confirmed responses, then axitinib would be recommended for further studies in this patient population. Results: Fifteen patients were screened, and eleven patients were initiated on protocol therapy. Median age was 63 years (range 37-88). Three patients (27%) had BRAF mutations. Objective response rate was 45.5% [95% confidence interval (CI), 16.7-76.6], comprised of one complete and four partial responses, with two patients ongoing. Median duration of response was 8 months (95% CI, 3.5-13.3). Stable disease was observed in one patient, with an overall disease control rate of 54.5% (95% CI, 23.3-83.2]. Median progression free survival was 4 months [95% CI, 2.8-8.5]. Median overall survival was 59 months [95% CI, 29.6-67.5]. The most frequently reported ( > 15%) nonhematologic, treatment-related adverse effects were hypertension, fatigue, and diarrhea. Conclusions: Axitinib showed single-agent activity among patients with stage III melanoma and had favorable effect as a neoadjuvant therapy. Axitinib was well tolerated and safety profiles were consistent with previous reports from previous studies in patients with melanoma. Axitinib alone or combined with other therapies merits further research. Clinical trial information: NCT01321437.