A phase I study of BAY 43–9006 and gefitinib in patients with refractory or recurrent non-small-cell lung cancer (NSCLC)

Abstract

3067 Background: Preclinical data in the A549 NSCLC xenograft model show that BAY 43–9006 (BAY) a dual-action Raf kinase and VEGFR inhibitor does not antagonize the effect of gefitinib. This phase I, single-center study was conducted to assess the safety and efficacy of this combination in patients (pts) with refractory or recurrent NSCLC. Methods: The dosing schedule was in two parts; part A, presented here, was to determine the optimal dose of BAY for use in part B, in which pharmacokinetic and pharmacodynamic parameters will be measured in 20 pts. Tumor response was assessed by RECIST. Results: 12 pts were treated (M:F = 6:6; median age 63 [range 46–78] years; ECOG status 0:1:2 = 5:6:1; number of prior systemic anti-cancer regimens 0:1:2:missing = 3:4:2:3). The first 6 pts received gefitinib 250 mg po qd with BAY 200 mg po bid, and the second 6 patients received gefitinib 250 mg po qd with BAY 400 mg po bid. The most common drug-related AEs were fatigue (75% of pts), diarrhea (75%) alanine aminotransferase (ALT; 58%), aspartate aminotransferase (AST; 42%), rash/desquamation (42%) and anorexia (42%), and were predominantly grade 1–2. Drug-related serious AEs were seen in 3 pts (diarrhea and ALT at BAY 200 mg bid, and dyspnea at BAY 400 mg bid). 1 (8%) partial response was achieved by a pt receiving BAY 200 mg bid and 8 (67%) pts had stable disease (SD) as best response (3 at BAY 200 mg bid, and 5 at 400 mg bid). Three patients died from disease progression and 4 are still on treatment. Conclusions: This study is the first to combine the novel targeted agent BAY with gefitinib. This combination was well-tolerated and led to tumor regression or SD in 9 of 12 pts. BAY 400 mg po bid combined with gefitinib 250 mg po qd is recommended for Part B of this study, which has accrued 7 patients. Results from part B will also be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer