Journal of Clinical Oncology · 2009 · 26 citations · 0 references
MedicineOncologyPharmacologyMolecular OncologyNeoplasiaOncogenesBiomarker ValidationBiomarkers In PathologyCancer BiomarkersCancer Molecular DiagnosticsMolecular Tumor ProfilingOncogenic Signaling PathwaysAdjuvant Clinical TrialsEgfr Mutation TestingErlotinib TherapyKras Mutation TestingPrimary Tumor AssessmentPrimary Tumor CharacterizationProtein Expression BiomarkersTumor-specific Biomarkers
7520 Background: RADIANT is a phase III trial comparing erlotinib 150 mg daily vs. placebo (2:1) in stage IB-IIIA NSCLC patients with EGFR-positive tumors (IHC and/or FISH), following complete surgical resection. Planned accrual is 945 patients. Correlative biomarker studies on primary tumor tissue, whole blood, and serum are key components of the study. Methods: Tumor tissue was evaluated by IHC for protein expression of EGFR (PharmDx Kit, Dako with + ≥ 1% positive tumor cells), by FISH for gene expression of EGFR (Vysis, Abbott), and by Wave HS for EGFR and Kras mutations. Results: Among 655 tissue samples analyzed, 96% were EGFR IHC+ and 74% EGFR FISH+. Of the 476 tissue samples analyzed to date for mutations (mut), 12% had activating EGFR and 19% had Kras mut. Preliminary comparisons suggest that EGFR mut rate increased while Kras mut rate decreased with tumor stage. EGFR mut occurred in 29/178 (16%) females (F) vs. 23/271 (8%) males (M), 19/57 (33%) Asians (A) vs. 33/392 (8%) non-Asians (NA), and 29/66 (44%) never smokers (NS) vs. 23/383 (6%) current or former smokers (S). The differences between A vs. NA and NS vs. S were significantly different (P <0.0001) for all comparisons made. Kras mut occurred in 40/180 (22%) F vs. 48/280 (17%) M, 4/57 (7%) A vs. 84/403 (21%) NA, and 3/68 (4%) NS vs. 85/392 (22%) S. The difference between A vs. NA and NS vs. S were significantly different (P ≤0.0389) for all comparisons made. In adenoca, 51/254 (20%) had EGFR and 79/261 (30%) had Kras mut, and in SCC, 0/157 (0%) had EGFR and 3/162 (2%) had Kras mut. One tumor sample demonstrated both an activating EGFR and Kras mut. Conclusions: Ongoing comprehensive biomarker assessment in the RADIANT population indicates successful sample collection and analysis. FISH positivity rates are greater than observed in late-stage tumors. Remaining results in this early-stage population are consistent with those observed in advanced-stage disease. Once complete, this study will provide a robust biomarker dataset on which to evaluate predictive and prognostic response markers, which may help determine who may benefit from treatment with erlotinib in the adjuvant setting. [Table: see text]