Phase II trial of imatinib (I) and docetaxel (D) in recurrent non-small cell lung cancer (NSCLC)

Abstract

18132Background: Second line monotherapy for NSCLC produces a response rate of 9% and a median survival of 7–8 months, regardless of the agent used. Emerging data suggest that combining an approved agent with an anti-angiogenesis inhibitor may improve efficacy in the salvage setting. Platelet Derived Growth Factor Receptor alpha (PDGFR-alpha) is involved in angiogenesis and its expression has been reported in 100% of adenocarcinoma (11/11) and 89% of squamous cell (16/18) lung cancer specimens in a small group sample. Preclinical models have shown that I inhibits PDGFR and may subsequently inhibit angiogenesis. In addition, I + D have additive anticancer activity. We initiated a phase II trial of I +D to evaluate the efficacy and safety of this combination regimen in recurrent NSCLC. Methods: Patients (pts)with pathologically confirmed NSCLC, measurable disease, no more than 1 previous platinum-based chemotherapy regimen, PS 0–1, clinically stable brain metastases and adequate organ function were eligible. Tumor samples, when available, were tested for PDGFR expression by immunohistochemistry. All pts received D 30mg/m2 intravenously weekly x 3 every 4 weeks and oral I 600mg daily for 4 cycles. Non- progressors after 4 cycles continued with I alone for a total of 12 months or until progression. Tumor response was assessed every 2 cycles. The primary endpoint was response rate. A Simon two-stage design was used with 16 patients in the first stage and accrual of a total of 32 patients planned. Results: Currently 15/16 patients for stage I of the protocol have been enrolled. A total of 24 cycles of combined I+D were given. Patient characteristics and toxicity data are described in the table below. Efficacy data is premature. Conclusion : I +D combination has been well tolerated in this relapsed population. A detailed toxicity, efficacy and PDGFR analysis will be presented.[Table: see text]No significant financial relationships to disclose.