Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Italy, 6 Department of Pathology, Radboud University Medical Center, Nijmegen/
Netherlands
Background: Molecular testing of the EGFR gene is required to predict
therapeutic response in non-small cell lung cancer (NSCLC). Although
routinely performed, analysis of tumor tissue is subject to limitations.
Analysis of circulating tumor DNA (ctDNA) in blood plasma may overcome
these barriers, and techniques to detect and quantify variants in ctDNA are
emerging. However, several key elements like sensitivity and specificity still
need to be addressed. This study evaluates the inter-laboratory performance
and reproducibility of the cobas ® EGFR Mutation Test v2 for the detection of
common EGFR variants in plasma. Methods: Fourteen laboratories from ten
European countries received two identical panels of 27 single-blinded plasma
members (Roche Molecular Systems, CA, USA). Samples were wild-type or
spiked with plasmid DNA containing seven common EGFR variants at six
predefined concentrations from 50-5000 target copies per mL (cp/mL). ctDNA
was extracted by the Roche cobas ® cfDNA Sample Preparation kit, followed
by duplicate analysis with the Roche cobas ® EGFR Mutation Test v2 kit. All
sites received hands-on training and two obligatory proficiency samples to
assure operator qualification. Statistical analyses were performed with SAS
9.4 (SAS Institute Inc., NC, USA). Results: In total, 0.8% (12/1512) and 0.2%
(3/1512) of runs were excluded due to protocol deviations or technical failures
respectively. The sensitivity was lowest for the c.2156G>C;p.(G719A) variant
with values of 80.4%, 69.6% and 89.1% at 50, 100 and 250 cp/mL respectively.
Besides 88.7% for the c.2573T>G;p.(L858R) variant at 50 cp/mL, sensitivities
for all other variants or concentrations varied between 96.3-100.0%
and improved for increasing cp/mL. Specificities were all 98.8%-100.0%.
Coefficients of variation (CV) indicate good intra-laboratory repeatability and
inter-laboratory reproducibility, but increased for decreasing concentrations.
Highest CV’s were reported for c.2156G>C;p.(G719A), c.2307_2308ins;Ex20Ins,
and c.2582T>A;p.(L861Q) at 50 cp/mL. Prediction models reveal a significant
correlation between the observed semi-quantitative index values (SQI)
and copy numbers in plasma for all variants. A systematic over- and
underestimation was observed for four different variants at 1000 and 5000
cp/mL respectively. Conclusion: This study demonstrates an overall robust
performance of the cobas® EGFR Mutation Test v2 in plasma, suggesting
a valuable and convenient addition to molecular tumor analysis in NSCLC.
Repeated tests are advisable in case of low SQI values to reduce the average
variation. Prediction models could be applied by future users to estimate
the plasma tumor load from the observed SQI value, taking into account the
possibility of systematic errors for high target copies.
Keywords: liquid biopsy, ctDNA, EGFR mutation analysis, plasma
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR CLINICAL –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-044 AFATINIB VERSUS GEFITINIB AS FIRST-LINE
TREATMENT FOR EGFR MUTATION-POSITIVE NSCLC PATIENTS
AGED ≥75 YEARS: SUBGROUP ANALYSIS OF LUX-LUNG 7
Keunchil Park 1 , Eng Huat Tan 2 , Li Zhang 3 , Vera Hirsh 4 , Ken O’Byrne 5 , Michael
Boyer 6 , James Chih-Hsin Yang 7 , Tony Mok 8 , Barbara Peil 9 , Angela Märten 9 , Luis
Paz-Ares 10
1 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
Korea, Republic of, 2 Medical Oncology, National Cancer Centre, Singapore,
Singapore/Singapore, 3 State Key Laboratory of Oncology in South China,
Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University,
Guangzhou/China, 4 McGill University, Montreal/QC/Canada, 5 Princess Alexandra
Hospital and Queensland University of Technology, Brisbane/QLD/Australia, 6 Chris
O’Brien Lifehouse, Camperdown/NSW/Australia, 7 National Taiwan University
Hospital and National Taiwan University Cancer Center, Taipei/Taiwan, 8 Key
Laboratory of South China, the Chinese University of Hong Kong, Hong Kong/China,
9 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein/Germany,
10 Hospital Universitario Doce de Octubre and Cnio, Madrid/Spain
Background: The irreversible ErbB family blocker afatinib and the reversible
EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment
of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7 trial, afatinib
significantly improved median progression-free survival (PFS; HR=0.73 [95%
CI, 0.57–0.95], p=0.017), objective response rate (70% vs 56%, p=0.008) and
time to treatment failure (TTF; HR=0.73 [95% CI, 0.58–0.92], p=0.007) versus
gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated
the efficacy and safety of afatinib versus gefitinib in patients aged ≥75 years
in a subgroup analysis of LUX-Lung 7 (NCT01466660). Methods: Treatmentnaïve
patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral
afatinib (40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation
type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary
endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS and
adverse events (AEs) by age (≥75/