Efficacy and safety of single-agent axitinib (AG-013736; AG) in patients (pts) with advanced non-small cell lung cancer (NSCLC): a phase II trial

Background: A correlation between vascular endothelial growth factor (VEGF), microvessel density, and prognosis has been reported in pts with NSCLC. AG 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 AG in pts with advanced NSCLC. Methods: Pts with stage IIIB or metastatic NSCLC received AG 5mg BID. Eligibility criteria included measurable disease and ECOG performance status of 0 or 1. A Simon 2-stage minimax design was used with 18 pts in the first stage plus an additional 14 in the second stage if 1/18 pts responded. The primary endpoint was response rate (RR) according to RECIST. Results: A total of 32 pts were enrolled: median age was 66.5yrs (range 39–80); histologies included adenocarcinoma (75%), squamous cell carcinoma (12.5%), and other (12.5%); 59% male/41% female; 78% received prior chemotherapy, 50% prior surgery, 50% prior radiotherapy, 9% investigational therapy, 3% immunotherapy, and 6% were treatment-naive. Mean duration of treatment was 2.6 months (mo) (range 0.03–12.9 mo). Three (9.4%) investigator confirmed responses were reported with a 95% confidence interval (CI) of 2, 25. Median duration of response was 8.3 mo (95% CI: 5.9, 10.6 mo). Median survival was 12.8 mo (95% CI: 9.9 mo, undefined) and progression-free survival was 4.9 mo (95% CI: 3.6, 7.0 mo). 30 (94%) pts discontinued treatment: lack of efficacy 21 pts (66%), adverse events 5 pts (16%), death 2 pts (6%), and other 2 pts (6%). Grade 3/4 toxicities (≥5%) were fatigue (22%), hypertension (9%), diarrhea (6%) and hyponatremia (6%). Conclusions: AG demonstrates single-agent activity in pts with advanced NSCLC. Therapy is well tolerated with manageable toxicity in this population. Further investigation in this setting is warranted.