First-Line TKI Use in EGFR Mutation-Positive NSCLC Jürgen Wolf, MD Medical Director, Center for Integrated Oncology Köln Department I of Internal Medicine University Hospital of Cologne Bonn, Germany

del19/L858R “common” mutations Pivotal Registration Trials With EGFR TKIs in EGFR Mutation-Positive NSCLC Study Treatment Regimen All EGFR mutations del19/L858R “common” mutations Median PFS Median OS IPASS[a] Asians with subgroup of EGFR mutations Gefitinib vs carboplatin + paclitaxel 9.5 vs 6.3 (HR, 0.48; 95% CI, 0.26-0.64) 21.6 vs 21.9 (HR, 1.00; 95% CI, 0.76-1.33) ------------------- EURTAC[b] European with all EGFR mutations Erlotinib vs cisplatin + docetaxel or gemcitabine 9.7 vs 5.2 (HR, 0.37; 95% CI, 0.25-0.54) 19.3 vs 19.5 (HR, 1.04; 95% CI, 0.65-1.68) LUX-Lung 3[c] International with all EGFR mutations Afatinib vs cisplatin + pemetrexed 11.1 vs 6.9 (HR, 0.58; 95% CI, 0.43-0.78) Not yet available 13.6 vs 6.9 (HR, 0.47; 95% CI, 0.34-0.65) CI = confidence interval; EGFR = epidermal growth factor receptor; HR = hazard ratio; NSCLC = non-small cell lung cancer; OS = overall survival; PFS = progression-free survival; TKI = tyrosine kinase inhibitor a. Fukuoka M, et al. J Clin Oncol. 2011;29(21):2866-2874; b. Rosell R, et al. Lancet Oncol. 2012;13(3):239-246; c. Yang JC, et al. ASCO 2012. Abstract LBA7500.

LUX-Lung 6 Trial: Afatinib vs Chemotherapy in EGFR Mutation-Positive NSCLC A multicenter, randomized, open-label, phase 3 trial in China, the Republic of Korea, and Thailand Patients with: Adenocarcinoma of the lung Presence of EGFR mutation in the tumor tissue Stage IIIB/IV No prior treatment with chemotherapy for advanced/metastatic disease No prior treatment with EGFR inhibitors Eastern Cooperative Oncology Group performance status 0 or 1 N = 364 Randomization 2:1 Afatinib 40 mg once daily Cisplatin 75 mg/m2 + gemcitabine 1000 mg/m2 IV day 1 + day 8, every 3 weeks Primary endpoint: PFS Wu YL, et al. ASCO 2013. Abstract 8016.

LUX-Lung 6 Trial: PFS Median PFS by independent review: 1-year PFS: 11.0 months for afatinib arm 5.6 months for chemotherapy arm 1-year PFS: 47% for afatinib arm 2% for chemotherapy arm Wu YL, et al. ASCO 2013. Abstract 8016.

LUX-Lung 6 Trial: Adverse Events Most common grade 3 adverse events associated with afatinib: Rash, 14.2% Diarrhea, 5.4% Stomatitis/mucositis, 5.4% Discontinuation rate due to treatment-related adverse events: 5.9% of patients on afatinib 39.8% of patients on chemotherapy Only 2% of patients on afatinib discontinued due to rash and none due to diarrhea Wu YL, et al. ASCO 2013. Abstract 8016.

Primary endpoint: PFS and disease control rate at 12 months LUX-Lung 7 Trial: Afatinib vs Gefitinib (Irreversible TKI vs Reversible TKI) Patients with Advanced adenocarcinoma of the lung Documented common EGFR mutations (del19 or L858R) First line (no prior treatment) Global study: 57 sites (currently recruiting) N = 264 Randomization Afatinib 40 mg Gefitinib 250 mg Primary endpoint: PFS and disease control rate at 12 months ClinicalTrials.gov. NCT01466660.

Take-Home Messages Patients must be tested for the EGFR mutation and, if positive, receive first-line EGFR TKI Significant improvements in PFS in first-line therapy of patients with EGFR mutation-positive NSCLC with EGFR TKI vs chemotherapy Significant improvement in quality-of-life parameters with EGFR TKI vs chemotherapy

Thank you for participating in this activity. To proceed to the Post-Test and Activity Evaluation, click on the Earn CME Credits link on this page.