1. 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

2. 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, )
21.6 vs 21.9
(HR, 1.00; 95% CI, )
EURTAC[b] European with all EGFR mutations
Erlotinib vs cisplatin + docetaxel or gemcitabine
9.7 vs 5.2
(HR, 0.37; 95% CI, )
19.3 vs (HR, 1.04; 95% CI, )
LUX-Lung 3[c]
International with all EGFR mutations
Afatinib vs cisplatin + pemetrexed
11.1 vs 6.9
(HR, 0.58; 95% CI, )
Not yet available
13.6 vs 6.9 (HR, 0.47; 95% CI, )
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): ; b. Rosell R, et al. Lancet Oncol.
2012;13(3): ; c. Yang JC, et al. ASCO Abstract LBA7500.

3. 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 Abstract 8016.

4. 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 Abstract 8016.

5. 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 Abstract 8016.

6. 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. NCT

7. 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

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