Exploratory analyses EGFR, kRAS mutations and other molecular markers in tumors of NSCLC patients (pts) treated with chemotherapy +/- erlotinib (TALENT)

Abstract

7028 Background: Erlotinib is a potent HER1/EGFR TKI that provides survival benefit as a single agent in 2nd and /3rd line NSCLC. The combination trial TALENT failed to show survival benefit for erlotinib and chemotherapy in 1st line NSCLC and has been described previously. The current objective was to analyze the relationship between biomarkers and treatment-related benefit. Tumor tissue was collected on 500 pts. Biomarker analyses by IHC, FISH, and sequencing were performed. Pts were assessed for survival, response, and TTP. Outcomes were correlated with biomarker data in retrospective subset analyses. Methods: EGFR and kRAS mutation analysis was performed on a set of 293 formalin-fixed tissue samples. Tumor cells were microdissected to extract tumor DNA, which was PCR amplified and sequenced for EGFR exons 18–21, 23 and kRAS exon 2 and 3. IHC analysis of biomarkers, such as EGFR, EGF, EGFRvIII, HER2, TGFα, and pAKT, as well as FISH assays for EGFR, HER2 and AKT were performed on tissue sections and/or tissue microarrays. Results: To date complete sequencing data is available for 191 (EGFR) and 163 (kRAS) samples, with the majority of EGFR mutations found in adenocarcinomas. EGFR mutations have been confirmed in 15 samples by independent PCR and sequencing reactions. For kRAS 24 mutations were confirmed. Correlations of response rates to mutation status were not statistically significant at the p = 0.05 level. Analyses of survival, TTP against mutation status will be presented. Gene amplification of EGFR, HER2 or AKT assessed by FISH was only seen in single samples. IHC showed mainly low expression rates for all assessed biomarkers except EGFR and pAKT: 57% showed pAKT 3+ staining. Statistical analysis on other biomarkers and combinations will be presented. Conclusions: Predictive biomarkers and their patterns may offer tailored therapy in NSCLC. Identification is still in an early phase. For this study no single marker was identified that consistently predicts tumor sensitivity or resistance to erlotinib. Tissue collection and analysis is recommended for future trials with erlotinib. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche, Hoffmann-La Roche AG, Roche Diagnostics GmbH AstraZeneca, Lilly Oncology, Roche Hofffmann-La Roche, Roche Abbott, AstraZeneca, Pierre Fabre, Roche AstraZeneca, Ligand, Lilly Oncology, Roche