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7503 Background: EGFR kinase inhibitors are effective in never-smokers with NSCLC especially in those harboring EGFR mutations. In a prior phase III study (TRIBUTE) ECP was associated with improved RR, PFS, and OS compared to CP but only in never-smokers. CALGB 30406 prospectively evaluated E and ECP in never/light former smokers with chemotherapy-naïve advanced lung adenoca and evaluated the impact of EGFR mutations on outcome. Methods: Chemotherapy-naïve, never, or light former (≤ 10 pack years, > 1 yr since cessation) smokers, with advanced lung adenoca were randomized to E alone (150 mg/day) or ECP (E 150 mg/day given continuously; C AUC = 6 and P (200 mg/m2) both q21 days) for 6 cycles followed by E. Primary endpoint was PFS in both arms. Collection of pretreatment tumor for assessment of EGFR mutations was mandatory. Results: Between 8/05 and 4/09 188 pts were accrued; 182 pts randomized (E=82; ECp=100) and treated. Baseline characteristics (E/ECP) were well balanced: Female: 61%/58%; Caucasian: 76%/84%; never smokers: 76%/77%; ECOG PS0: 61%/46%; adenoca: 87%/80%. Median number of cycles: E:6; ECP:7.Toxicity: Grade 3/4 hematologic toxicity: E: 1/0 (1%); ECP: 28/20 (48%). Grade 3/4 nonhematologic toxicity: E: 17/2 (23%); ECP: 39/11 (50%). EGFR genotyping possible in 172 pts (95%). EGFR mutant/wild type: 67 (39%)/105 (61%). Exon 19:36; L858R:31. Outcomes are shown in the Table. Median follow-up is 25 mos. 53% of pts have died in both arms. Primary endpoint was met in both arms. EGFR mut pts had a significantly better RR (p < 0.0001 both arms), PFS (p < 0.0001 both arms) and OS (p = 0.0027 E; p = 0.0009 ECP) than EGFR WT pts. Conclusions: E and ECP have similar efficacy, but E is less toxic, in predominantly Caucasian never smokers with advanced NSCLC. EGFR mutations identify patients most likely to benefit from E and ECP. E (n = 82) RR PFS months (80% CI) OS months (80% CI) All pts 34% 6.7 (4.7-8.2) 24.0 (18.4-27.6) EGFR mutation (n = 32) 66% 16.4 (12.1-23.8) 27.6 (24.0-42.8) EGFR WT (n = 48) 8% 2.8 (1.6-4.1) 15.4 (11.2-19.9) ECP (n = 100) All pts 47% 6.0 (5.6-7.3) 19.6 (14.7-24.6) EGFR mutation (n = 35) 69% 17.2 (11.1-27.6) 39.0 (39.0-NR) EGFR WT (n = 57) 31% 4.8 (4.2–5.6) 13.7 (10.0-18.0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, AVEO, Boehringer Ingelheim, Genentech, OSI Pharmaceuticals, Roche, Syndax Pharmaceuticals Gatekeeper Pharmaceuticals Genentech, Lilly, Roche, sanofi-aventis Abraxis BioScience, Celgene, Genentech, Lilly, Pfizer, sanofi-aventis Genzyme
Jänne et al. (Thu,) studied this question.