Transcript First-Line TKI Use in EGFR Mutation-Positive NSCLC

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
Pivotal Registration Trials With EGFR TKIs in
EGFR Mutation-Positive NSCLC
Treatment
Regimen
Study
IPASS[a]
Gefitinib vs
Asians with
carboplatin +
subgroup of
EGFR mutations paclitaxel
EURTAC[b]
European with
all EGFR
mutations
LUX-Lung
3[c]
International
with all EGFR
mutations
Erlotinib vs
cisplatin +
docetaxel or
gemcitabine
Afatinib vs
cisplatin +
pemetrexed
All EGFR mutations
Median PFS
Median OS
9.5 vs 6.3
21.6 vs 21.9
(HR, 0.48;
95% CI, 0.26-0.64)
(HR, 1.00;
95% CI, 0.76-1.33)
del19/L858R “common”
mutations
Median PFS
Median OS
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9.7 vs 5.2
19.3 vs 19.5
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(HR, 0.37;
95% CI, 0.25-0.54)
(HR, 1.04;
95% CI, 0.65-1.68)
11.1 vs 6.9
Not yet available
13.6 vs 6.9
Not yet available
(HR, 0.58;
95% CI, 0.43-0.78)
(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:
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–
–
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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
Cisplatin 75 mg/m2 + gemcitabine 1000 mg/m2
40 mg once daily
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:
– 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.
LUX-Lung 7 Trial: Afatinib vs Gefitinib
(Irreversible TKI vs Reversible TKI)
• Patients with
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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
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