EGFR mutations and pAKT expression as potential predictors of gefitinib efficacy in non-small cell lung cancer (NSCLC) patients (pts)

Abstract

7077 Background: Activating mutations in exons 18–21 of the EGFR gene have been found in tumors from NSCLC pts that respond to gefitinib (GEF). The goal of this study was to assess EGFR mutations, as well as expression of EGFR and related molecules by immunohistochemistry (IHC) as predictors of GEF efficacy. Methods: A total of 143 consecutive pts were enrolled in the Expanded Access Trial; 7 pts died and 1 withdrew consent prior to starting treatment. Only pts with > 1 week of therapy were included for analysis. IHC was performed for 64 pts with evaluable tissue specimens. Tissue from 34 pts was analyzed for activating mutations by sequence analysis. Fisher’s Exact Test was used to evaluate associations. Results: 126 pts (64 female, 62 male; median age 68; 67 adenocarcinomas, 59 others) received GEF; median follow-up was 169 days. Overall response rate was 6.4% (1CR, 7PR), and 51 pts (40%) had stable disease (SD). Median Kaplan-Meier survival and progression-free interval (PFI) were 172 and 59 days, respectively. EGFR mutations were found in 9 of 34 tumors evaluated. None of the tumors from 9 pts with PD had mutations; 6/8 (75%) pts with CR or PR, and 3/14 (21%) pts with SD had detectable mutations. A significant association (p<.002) was observed between mutation and response. Median PFI for pts with and without EGFR mutations was 274 and 117 days, respectively (p<.05); no significant difference in survival was observed. Significant positive associations with response were also observed for EGFR (p<.02) and ErbB2 expression (p<.07). Median survival for pts with and without pAKT expression was 373 and 150 days, respectively (p<.02). Significant positive associations with pAKT expression were observed for EGFR (p<.02), ErbB2 (p<.003), pMAPk (p<.04), and IGF-1r (p<.06) expression. Conclusions: Defining molecular profiles predictive of GEF efficacy is still at an early stage. EGFR activating mutations, and detectable EGFR, pAKT, and ErbB2 expression may have predictive value for GEF response; pAKT may have predictive value for survival. Further investigation of molecular markers and mutations is warranted due to the clinical implications with respect to pts with NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, CTI, Genentech, GlaxoSmithKline, Lilly Oncology, Pfizer Abbott Laboratories, Amgen, AstraZeneca, Genentech, Lilly Oncology, Pfizer AstraZeneca, Bristol-Myers Squibb, CTI, Genentech, GlaxoSmithKline, Lilly Oncology, Pfizer AstraZeneca, Bristol-Myers Squibb, CTI, Genentech, GlaxoSmithKline, Lilly Oncology, Pfizer