Phase 2 Trial of Linifanib (Abt-869) in Patients with Advanced Non-Small Cell Lung Cancer

Introduction: This study assessed activity and safety of linifanib (ABT- 869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, in patients with locally advanced or metastatic non-small cell lung cancer. Methods: In this open- label trial (NCT00517790), patients who received one to two prior lines of systemic therapy were randomized to oral linifanib 0.10 mg/kg (low dose) or 0.25 mg/kg (high dose) once daily. Tumor responses were assessed by independent central imaging review every 8 weeks. The primary end point was progression -free rate at 16 weeks. Secondary end points included objective response rate, time to progression, progression- free survival, and overall survival. Safety was also assessed. Results: Between August 2007 and October 2008, 139 patients were enrolled; 60% had two or more prior regimens, and 88% had nonsquamous cell carcinoma. The objective response rate (low dose and high dose) was 5.0% (3.1 and 6.8 %), progression-free rate at 16 weeks was 33.1% (32.3 and 33 .8%), median time to progression was 3.6 months (3.6 and 3.7 months), median progression- free survival was 3.6 months (3 .5 and 3.6 months), and median overall survival was 9.0 months (10.0 and 8.3 months). The most common linifanib- related adverse events were fatigue (42%), decreased appetite (38%), hypertension (37%), diarrhea (32%), nausea ( 27%), palmar-plantar erythrodysesthesia (24%), and proteinuria (22%). These events were more common in the high -dose group. The most common linifanib-related grade 3 or 4 adverse event was hypertension (14%). Conclusions: Linifanib is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.