Potential molecular prognostic factors in non-small cell lung cancer (NSCLC) patients treated with gefitinib

Abstract

7089 Background: Phase II studies have shown that gefitinib produces a 10% response rate in previously treated patients(pts) with NSCLC. Little is known about the relationship between molecular profiles and NSCLC response to gefitinib. The goal of this study was to assess IHC for EGFR, IGFR, VEGF expression and FISH for EGFR amplification as predictors of response to gefitinib. Methods:A total of 143 consecutive pts were enrolled in the Expanded Access Trial; seven pts died prior to starting gefitinib; one withdrew consent before treatment. Only pts who had > 1 week of therapy were included in the analysis. Results:126 pts(64 female, 62 male, median age 68, 67 adenocarcinomas/59 others) received gefitinib; median follow-up was 169 days. Overall response rate was 5.6%(1CR,6PR) and 24 pts(19%) had stable disease(SD). Median Kaplan-Meier survival and progression-free interval (PFI) were 172 and 59 days, respectively. The Fisher's Exact Test was used to evaluate associations. A greater proportion of pts with adenocarcinoma responded or had stable disease(p=.08). Of the 126 pts treated, 52 had tissue available for molecular profiles. None of the 28 pts who lacked expression of EGFR by IHC responded to gefitinib compared to 5 responses (CR+PR) in the 24 patients with EGFR positive tumors (p<.02). Median PFI for pts with and without EGFR expression was 102 and 75 days, respectively (Log-Rank p=.2563). For 21/50 pts with both EGFR expression and chromosome copy 7 number (FISH ≥2.5, five (24%) responded (CR+PR) compared to 0% of the 29 other pts (p<.001). 11 pts had EGFR amplification by FISH (≥1.5,Vysis SpectrumOrange-LSI EGFR probe) which was associated with EGFR expression (p=.064), and adenocarcinoma (p<.09).There was a positive association between EGFR expression and IGFR expression (p<.09) Conclusions:Defining molecular profiles for response to gefitinib is still at an early stage. Detectable EGFR expression and chromosome 7 copy number may have predictive value for response in pts treated with gefitinib. The association between EGFR expression IGFR expression in this small study suggests that further investigation of molecular markers is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb AstraZeneca