Pilot phase II study of preoperative gefitinib in early stage non-small cell lung cancer with assessment of intratumor gefitinib levels and tumor target modulation

Abstract

7603 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) can provide clinical benefit in advanced non-small cell lung cancer patients. Here we examined the effect of single agent gefitinib in patients with early stage NSCLC with additional assessment of plasma and tumor concentrations of gefitinib. Previous studies have suggested considerably higher tumor concentrations of gefitinib compared to levels identified in blood, yet the results in human lung cancers is unknown. Methods: We conducted a pilot phase II study of a 28 day preoperative course of gefitinib 250 mg PO daily followed by surgical resection for patients with stage IA to selected IIIA non-small cell lung cancer. Response was assessed by RECIST using CT and changes in FDG metabolism were assessed using PET. Tumor penetration of gefitinib was assessed in surgically resected tumor samples along with plasma assessment on day 28. Results: Sixteen patients (7 men, 9 women) completed therapy on protocol and all who started on gefitinib were able to undergo a complete surgical resection. There were 0/16 objective responses (CR/PR), 14/16 SD, and 2/16 PD. Three of the 6 patients had more than 20% reductions in FDG SUVmax assessed by PET scanning. Day 28 plasma concentrations of gefitinib averaged 531 ± 344 nM (range 65 to 1,211 nM) while tumor concentrations of gefitinib averaged 33,108 ± 44,312 nM (range 474 to 134,669 nM). Conclusions: Our results demonstrate that NSCLC tumor penetration of gefitinib is much higher than concentrations found in plasma. Assessment of pharmacodynamic markers including tumor EGFR and downstream signaling pathways is ongoing. PET scanning may be an early marker of clinical benefit of EGFR TKI. No significant financial relationships to disclose.