Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Median PFS after treatment with 3rd-TKI was 3.4 months if tumor testing is
T790M- versus 9.7 months if T790M+. Because urine testing can be used in
patients for whom biopsy cannot be performed or when tissue testing reveals
indeterminate results, PFS and OS were slightly increased using the UTS.
UTS resulted in avoidance of a biopsy procedure, potential complications,
and tissue-based molecular testing in approximately 48% of patients,
leading to a 2- to 10-fold total cost savings relative to the unit cost for a urine
test. Within the robust variations in input parameters, the cost of a biopsy
procedure/complications and tissue-based molecular testing were the most
influential factors. Conclusion: UTS is a dominant scenario to TTS by saving
costs and improving patient experience (e.g., PFS/OS, and reduction in biopsy
related complications). This result is based on LEVEL I evidence from a large,
randomized trial that showed PFS is similar among patients regardless of
urine versus tissue testing for T790M mutation status.
Keywords: NSCLC, T790M, liquid biopsy, Health Economics
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-011 COMPARISON OF FOUR LEADING TECHNOLOGIES FOR
DETECTING EGFR MUTATIONS IN CIRCULATING TUMOR DNA FROM
PATIENTS WITH NON-SMALL CELL LUNG CARCINOMA
Xiaozheng Kang 1 , Ting Xu 2 , Guobin Xu 3 , Ke-Neng Chen 4
1 Department of Thoracic Surgery I, Peking University Cancer Hospital and
Institute, Beijing/China, 2 Department of Clinical Laboratory, Key Laboratory
of Carcinogenesis and Translational Research (Ministry of Education), Peking
University Cancer Hospital and Institute, Beijing, China, Beijing/China,
3 Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and
Translational Research (Ministry of Education), Peking University Cancer Hospital
and Institute, Beijing/China, 4 Department of Thoracic Medical Oncology, Key
Laboratory of Carcinogenesis and Translational Research (Ministry of Education),
Peking University Cancer Hospital and Institute, Beijing/China
Background: This study aimed to assess the ability of different technology
platforms to detect epidermal growth factor receptor (EGFR) mutations
including L858R, E19-dels, T790M, and G719X from circulating tumor DNA
(ctDNA) in patients with non-small cell lung cancer (NSCLC). Methods: Plasma
samples were collected from 20 patients with NSCLC including detailed
clinical information along with data regarding treatment response. ctDNA
was extracted from 10 mL plasma using the QIAamp Circulating Nucleic Acid
Kit (Qiagen). Extracted ctDNA was analyzed using two real time-amplification
refractory mutation system-quantitative PCR platforms (cobas® EGFR
Mutation Test: cobas; and AmoyDx® EGFR 29 Mutations Detection Kit:
ADx), one digital platform (Droplet Digital TM PCR, ddPCR: Bio-rad), and one
next-generation sequencing platform (firefly NGS: Accuragen). Results: If a
positive result was obtained from any one of the four platforms, the sample
was categorized as positive. We identified 15 EGFR mutations in 20 patients
with NSCLC using the four platforms, for which 7, 11, 10, and 12 mutations
were detected by ADx, cobas, ddPCR, and firefly NGS, respectively. Among
the 15 EGFR mutations, six and seven EGFR alterations demonstrated an
allele frequency of more or less than 1% (group A or B, respectively), and two
exhibited unknown allele frequency. In group A, 5, 5, 5, and 6 EGFR mutations
were detected by ADx ,cobas, ddPCR, and firefly NGS, respectively. The
positive coincidence rate of any two platforms ranged from 66.7% to 100%
and the kappa value varied from 0.787 to 1.000 in group A. In group B, 1, 5, 5,
and 6 EGFR mutations were detected and the positive coincidence rate of
any two platforms ranged from 16.7% to 100% and the kappa value varied
from 0.270 to 1.000. The output of cobas, ddPCR, and firefly NGS were highly
correlated, whereas ADx displayed weak concordance with these three
platforms in group B. In addition, we identified 75 wild-type loci when EGFR
alleles identified as negative by one or more platforms were considered as
negative. ADx, cobas, ddPCR, and firefly NGS uncovered 73, 69, 70, and 68
EGFR wild-type loci, respectively. The concordance and negative coincidence
rates between any two platforms were over 90%. Conclusion: The detection
rate and concordance were probably affected by the abundance of EGFR
mutations and the sensitivity of different platforms. Three platforms,
including cobas, ddPCR, and firefly NGS, exhibited higher positive coincidence
and detection rates when the allele frequency was lower than 1%.
Keywords: Non-small-cell lung cancer, Epidermal growth factor receptor,
Circulating Tumor DNA, next-generation sequencing
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-012 LONGITUDINAL MONITORING OF CTDNA EGFR
MUTATION BURDEN FROM URINE CORRELATES WITH PATIENT
RESPONSE TO EGFR TKIS: A CASE SERIES
Nishan Tchekmedyian 1 , Raja Mudad 2 , Eric Haura 1 , Fernando Blanco 3 , Victoria
Raymond 3 , Mark Erlander 3 , Jordan Garst 4 , David Berz 4
1 H. Lee Moffitt Cancer Center and Research Institute, University of South Florida,
Tampa/FL/United States of America, 2 Division of Hematology-Oncology, Sylvester
Comprehensive Cancer Center, University of Miami School of Medicine, Miami/FL/
United States of America, 3 Medical and Scientific Affairs, Trovagene, San Diego/
United States of America, 4 Beverly Hills Cancer Center, Beverly Hills/United States
of America
Background: Circulating tumor DNA (ctDNA) are short DNA fragments
released into the systemic circulation by rapid cell turnover, and excreted
into the urine. Urinary ctDNA-based detection of oncogenic mutations is a
non-invasive modality that can help in clinical decision-making, especially
when tissue biopsies are not available. When conventional imaging modalities
are inconclusive, quantitative assessment of systemic ctDNA burden has the
potential to assess response to therapy. In this case series we assessed EGFR
mutation status at baseline and at intervals following administration of
tyrosine kinase inhibitor (TKI) therapy to determine whether EGFR systemic
mutation load correlated with disease burden and therapeutic response.
Methods: Four patients on anti-EGFR (TKI) were prospectively monitored
for quantitative assessment of systemic mutant allele burden of activating
and resistance EGFR mutations (Exon 19 deletions, L858R and T790M) in
urine. EGFR mutations were quantitatively interrogated by short footprint
mutation enrichment PCR followed by next-generation sequencing assays.
Systemic mutant allele burden was compared to assessment of tumor burden
computed by standard imaging modalities. Results: Patients 1, 2, and 3
were originally diagnosed with EGFR-positive NSCLC. Targeted molecular
testing of systemic urine ctDNA revealed high EGFR mutation burden and
the presence of the T790M resistance mutation at the time of progression
on TKI therapy (>550 copies/10 5 genome equivalents (GEq)). Interestingly,
the extent of radiographic progression in patient 3 was not completely clear,
and urinary T790M along with clinical assessment of pain helped determine
progression prior to obtaining pleural effusion results. After initiation of a 3rd
generation TKI (patient 1: ASP8273, patients 2 and 3: osimertinib), all patients
experienced an appreciable decrease in the EGFR mutation burden, which was
consistent with clinical improvement prior to radiographic imaging. Patient 4
presented with multiple lung nodules at diagnosis and a high systemic L858R
mutant allele burden (>550 copies/100,000 GEq). Two months after initiation
of first-line TKI, the main lesion and lymph nodes slightly improved, but the
lung nodules progressed. The high systemic L858R burden persisted at the
same level as pre-therapy. Conclusion: Urinary ctDNA-based quantitative
assessment of systemic EGFR mutant allele burden is a non-invasive
molecular diagnostic testing modality that correlates with tumor burden and
response to therapy.
Keywords: ctDNA (circulating tumor DNA), Monitoring, tyrosine kinase
inhibitor (TKI)
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-013 EVALUATION OF LUNG SPECIFIC GPA SCORE IN
ADENOCARCINOMA PATIENTS WITH BRAIN METASTASIS AND
EGFR ACTIVATING MUTATION
William Kao 1 , Audrey Dugué 1 , Pascal Dô 1 , Catherine Dubos 1 , Delphine
Lerouge 1 , Serge Danhier 1 , Nicolas Richard 2 , Radj Gervais 1
1 Baclesse, Caen/France, 2 CHU, Caen/France
Background: The lung specific GPA score is an index, commonly used for
patients with non-small cell lung carcinoma (NSCLC) and brain metastasis
(BM) in order to predict overall survival (OS) with the help of four easy-to-use
items: age at the diagnosis of the brain metastasis; Karnofsky Performance
Status (KPS), presence of extra cranial metastasis (ECM) and number of
brain metastasis (Sperduto PW et al. J Clin Oncol 2012; 30:41925). However,
this tool might not be appropriate to patients harboring EGFR activating
mutations, which are known to have better prognosis than those with
no activating mutations. The goal of our study was to determine if the
Lung specific GPA score is adapted to population with these mutations.
Methods: We retrospectively analyzed 108 Caucasians patients diagnosed
with NSCLC between 2000 and 2014. Clinical features, systemic treatments
(chemotherapy or EGFR tyrosine kinase inhibitors) and local brain treatment
S626 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017