Efficacy and Safety of Single-Agent Axitinib (AG-013736; AG) in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC): A Phase II Trial

Abstract

Background A correlation between vascular endothelial growth factor (VEGF), microvessel density, and prognosis has been reported in patients with NSCLC. Axitinib is a specific VEGF receptor (VEGFR) inhibitor with picomolar potency against VEGFR-1, -2 and -3. This is an open-label, multicenter, phase II study examining the efficacy and safety of single-agent axitinib in patients with advanced NSCLC. Patients and Methods Patients with stage IIIB or metastatic NSCLC received axitinib 5 mg twice a day. Eligibility criteria included measurable disease and Eastern Cooperative Oncology Group performance status of 0/1. A Simon 2-stage minimax design was used with 18 patients in the first stage plus an additional 14 patients in the second stage, if 1 of the 18 patients has a response. The primary endpoint was response rate according to Response Evaluation Criteria in Solid Tumors. Results A total of 32 patients were enrolled: median age was 66.5 years (range, 39-80 years); histologies included adenocarcinoma (75%), squamous cell carcinoma (12.5%), and other (12.5%). Fifty-nine percent were male, and 41% were female; 78% received previous chemotherapy, 50% previous surgery, 50% previous radiation therapy, 9% investigational therapy, 3% immunotherapy, and 6% were treatment naive. Mean duration of treatment was 2.6 months (range, 0.03-12.9 months). Three (9.4%) investigator-confirmed responses were reported with a 95% confidence interval (CI), 2-25 responses. Median duration of response was 8.3 months (95% CI, 5.9-10.6 months). Median survival was 12.8 months (95% CI, 9.9 months, undefined), and progression-free survival was 4.9 months (95% CI, 3.6, 7.0 months). Thirty patients (94%) discontinued treatment because of lack of efficacy (n = 21; 66%), adverse events (n = 5; 16%), death (n = 2; 6%), and other (n = 2, 6%). Grade 3/4 toxicities (≥ 5%) were fatigue (22%), hypertension (9%), diarrhea (6%) and hyponatremia (6%). Conclusion Axitinib demonstrates single-agent activity in patients with advanced NSCLC. Therapy is well tolerated with manageable toxicity in this population. Further investigation in this setting is warranted.