Abstracts

Abstract

Purpose/Objective(s): Pazopanib is an oral multikinase inhibitor approved in advanced renal cell cancer. Preliminary activity was seen in non‐small‐cell lung cancer (NSCLC) where preoperative pazopanib reduced tumors in 86% of patients (pts) with stage I‐II disease (Altorki JCO 2010). Pazopanib has been safely combined with erlotinib in a phase I study (Dy ESMO 2009). Pts with refractory NSCLC were treated with pazopanib and erlotinib (PE) or placebo and erlotinib (E) in this multicenter double‐blind randomized phase II study. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate, toxicity, and overall survival (OS). Blood and tumor samples were collected for biomarker analyses. Materials/Methods: Pts with IIIB/IV NSCLC, an ECOG PS 0‐1, measurable disease, following 1‐2 lines of chemotherapy were eligible. Pts were randomized 2:1 to erlotinib 150mg PO daily and pazopanib 600mg PO daily or erlotinib and placebo until disease progression or unacceptable toxicity with imaging every 8 weeks. Results: 192 pts were enrolled (PE=127, E=65) from 2/2010 to 2/2011. Baseline characteristics were well balanced: median age 66 yrs (35‐88 yrs), 54% male, 63% second‐line. The median treatment duration per arm was 2 months. PE resulted in a statistically significant improvement in PFS: HR 0.59 (95% CI, 0.43‐0.83); median 2.6 (PE) and 1.8 (E) months; P=.0016. The partial response and stable disease rates were 6% and 39% (PE) and 0 and 35% (E). OS was similar between arms: HR 1.1 (0.77‐1.55); median 6.8 (PE) and 6.7 months (E); P=.61. PE resulted in statistically significant improvements in PFS in pts with proteomic classified VeriStrat good tumors (HR 0.49). Additional EGFR mutation, EGFR FISH, KRAS mutation, MET FISH, cytokine and angiogenic factor analyses will be presented. Grade 3/4 hematologic toxicity was rare (<4%) per arm. Severe nonhematologic toxicities were: diarrhea (PE 19%, E 9%), fatigue (PE 20%, E 14%), and proteinuria (PE 5%, E 0). Elevated hepatic enzymes occurred with greater frequency in the treatment arm occurring in up to 3% of pts and reversed with therapy cessation. Conclusions: The combination of pazopanib and erlotinib improved PFS over erlotinib alone in this double‐blind randomized phase II study. PFS advantages were seen in several biomarker‐defined subgroups. Additional study of pazopanib in NSCLC is warranted.