Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
naive cases as well as those who developed clinical resistance to tyrosine
kinase inhibitors. The later cases were examined for previous known and new
T790M mutations using highly sensitive Droplet Digital PCR. Where ever
feasible the results were compared to the secondary biopsy findings, duration
of development of new T790M mutation and its serial plasma quantification
results. Results: 20 Treatment naive biopsy positive DEL19 /L858R cases were
tested for cell free DNA. All cases were positive with values ranging from
.04% to 24%. 19 cases were checked for primary and secondary mutations
on progression of disease. 12 cases showed secondary mutation along with
primary mutation. The values of T790M mutation ranged from 0.04% to
4.5%. We also had 3 cases with biopsy and cell free correlation of secondary
mutation. None of them correlated. Conclusion: Droplet digital PCR is a robust
platform to detect the primary driver EGFR mutations and can be used as a
substitute / addendum to biopsy for initiating early treatment. It also appears
to be too sensitive for detection of secondary T790M mutations. However
response to treatment in patients with minimal cell free T790M values in
plasma may need to be further investigated for clinical utilization of this
platform.
Keywords: T790M, EGFR, droplet digital PCR, cell free DNA
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-023 PHYSICIAN PATTERNS OF CARE IN PATIENTS WITH
EGFR MUTATION+ NSCLC: AN INTERNATIONAL SURVEY INTO
TESTING AND TREATMENT CHOICE
Bernd Tischer 1 , Edward Kim 2 , Matthew Peters 3 , Vera Hirsh 4
1 Marketing Insights, Kantar Health, Muenchen/Germany, 2 Solid Tumor Oncology,
Levine Cancer Institute, Carolinas Healthcare System, Charlotte/NC/United States
of America, 3 Reespiratory Medicine, Concord Hospital, Concord/NSW/Australia,
4 Department of Medical Oncology, McGill University, Royal Victoria Hospital,
Montreal/Canada
Background: (Applied for Late-Breaking Abstract Status) IASLC guidelines
recommend EGFR mutation testing should be performed at diagnosis of
advanced NSCLC to guide treatment decisions. In 2015 an international survey
concluded that not all patients were tested or received test results before
treatment initiation. This varied between countries and across regions.
The aim of a follow-up survey in 2016 was to assess testing rates and HCP
treatment choice in advanced NSCLC to identify improvements and changes
compared to 2015. Methods: Online survey of 707 oncologists in 11 countries
(Canada, China, France, Germany, Italy, Japan, South Korea, Spain, Taiwan,
UK, USA) between July - August 2016. China was newly added in 2016. For
better comparison with 2015 results, China was excluded from the primary
results focus Results: Globally*, physicians requested EGFR mutation testing
prior to first-line therapy of stage IIIb/IV NSCLC in 80% of patients. However,
18% of ordered tests were not received prior to deciding first-line therapy; an
improvement on 2015 with 23%. Excluding histology, the main reasons for not
testing prior to first-line therapy were insufficient tissue, poor performance
status and long turnaround time. While turnaround time significantly reduced
year-on-year (2016: 21% vs. 2015: 30%), globally* 24% of patients receive
test results after more than 10 business days. Globally* 79% (2015: 80%) of
patients with mutations (M+) were treated with tyrosine kinase inhibitors
(TKIs), with large country variations on treatment preference (minimum 68%
Germany; maximum 98% Taiwan). Prolonging of survival/extending life (54%*)
was deemed the most important therapy goal in first-line treatment. 74%*
of physicians stated that a clinically relevant increase in overall survival was
the most important treatment attribute when choosing a first-line therapy,
closely followed by an increase in progression-free survival (68%) and strong
improvement of health related quality of life (66%). Perceived differences
between TKIs were reported by 49% of physicians. Further detail will be
presented at the congress.
*Global figures excluding China Conclusion: While year-on-year improvements
in EGFR testing rates, and availability of test results prior to first-line
therapy are seen, a large proportion of EGFR M+ NSCLC patients are still not
receiving targeted treatment with TKIs based on mutation status. Incomplete
implementation of guidelines is still observed. The main barriers to testing,
including receiving results in time, must be addressed if treatment equality
for all eligible patients can be achieved. Physician education and closer
guideline concordance are key steps to further improve outcomes.
Keywords: NSCLC, EGFR, TKIs
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-024 DYNAMICS OF EGFR MUTATIONAL LOAD IN URINE AND
PLASMA CORRELATES WITH TREATMENT RESPONSE IN ADVANCED
NSCLC
Jhanelle Gray 1 , Benjamin Creelan 1 , Tawee Tanvetyanon 1 , Scott Antonia 1 ,
Charles Williams 1 , Karen Johnson 1 , Christine Sigua 1 , Jongphil Kim 2 , Richard
Reich 2 , Braydon Schaible 2 , Cecile Rose Vibat 3 , David Gustafson 3 , Sandeep
Pingle 3 , Mark Erlander 3 , Vlada Melnikova 3 , Eric Haura 1
1 Department of Thoracic Oncology, Moffitt Cancer Center, Tampa/FL/United States
of America, 2 Department of Biostatistics, Moffitt Cancer Center, Tampa/FL/United
States of America, 3 Trovagene, San Diego/CA/United States of America
Background: NSCLC is a heterogeneous and dynamic disease where testing for
key mutations is essential. With the emergence of clonal resistance, obtaining
serial biopsies to assist in the real-time treatment decision-making has proven
challenging. Molecular assessments of circulating tumor (ct)DNA has been
previously shown feasible utilizing blood specimens. Here we additionally
investigated the utility of serial urine ctDNA analysis in NSCLC. Methods:
This is a prospective observational study of patients with non-squamous,
tissue-confirmed EGFR, KRAS or ALK mutant NSCLC preparing to receive a
systemic treatment regimen. Urine and blood specimens were collected at
baseline, on treatment and at progression for ctDNA analyses. The primary
endpoints were correlation between ctDNA and tumor-based molecular
results, and measurable change in ctDNA with response by RECIST v1.1. Blood
and urine samples were sent to Trovagene for DNA extraction and mutation
enrichment NGS. Results: Of the 34 patients enrolled thus far, interim
blinded analysis of EGFR activating mutations (L858R, exon 19 deletions)
was conducted in 20 patients with EGFR-positive tumors. Of 20 patients,
17 (85%) had detectable concordant EGFR mutation in pre-treatment urine
and/or plasma. Of 11 patients with matched serial ctDNA samples, detectable
EGFR mutation signal was observed in pre-treatment urine and/or plasma
of 9 patients. These 9 patients received first to sixth line treatment with
single EGFR TKI (n=3), combination TKIs (n=3), chemotherapy (n=1), immune
checkpoint inhibitors alone (n=1) or in combination with TKI (n=1). In 9 of 9
patients, changes in ctDNA levels from baseline to cycle 2 day 1 on therapy
correlated with best response to treatment: a 100% decrease in urine and
plasma EGFR mutation levels was observed in 6 of 6 patients with partial
response (PR, n=3) or stable disease (SD, n=3), while less than a 90% decrease
or an increase in urine and plasma EGFR levels was observed in patients with
progressive disease (PD, n=3). Conclusion: Mutation enrichment NGS testing
by urine and plasma ctDNA correctly identified EGFR activating mutations
in 85% of patients. Monitoring EGFR levels in urine/plasma enabled accurate
assessment of response in advance of radiographic evaluation and regardless
of therapy type in 100% of patients, with cut-point of a 90% decrease in EGFR
load discriminating between patients with disease control (PR or SD) and
patients with progressive disease. With continued enrollment, our study
aims to further investigate clinical utility of urine and plasma ctDNA for early
detection of resistance and discontinuation of inefficient therapy.
Keywords: ctDNA, lung cancer, EGFR, urine
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-025 RAPID AND HIGHLY SENSITIVE EGFRDELEX19 AND
KRAS EXON 2 MUTATION DETECTION IN EBUS-TBNA SPECIMEN OF
LUNG ADENOCARCINOMA
Filiz Oezkan 1 , Thomas Herold 2 , Kaid Darwiche 1 , Wilfried Eberhardt 2 , Daniel
Christoph 2 , Karl Worm 3 , Lutz Freitag 4 , Kurt Schmid 3 , Thomas Hager 3 , Frank
Breitenbuecher 2 , Martin Schuler 2
1 Department of Interventional Pneumology, Ruhrlandklinik, West German Lung
Center, University Duisburg-Essen, Essen/Germany, 2 Department of Medical
Oncology, University Hospital Essen, West German Cancer Centre, University
Duisburg-Essen, Essen/Germany, 3 Institute of Pathology, University Duisburg-
Essen, University Hospital Essen, Essen/Germany, 4 Department of Pulmonology,
University of Zurich, Zürich/Switzerland
Background: First-line treatment with afatinib prolongs overall survival
in patients with metastatic non-small-cell lung cancer (NSCLC) harboring
EGFR exon 19 deletion mutations. Conversely, somatic KRAS mutations
are negative predictors for benefit from EGFR-targeting agents. Rapid
availability of these biomarker results is mandatory to prevent delayed or
inferior treatments. Endobronchial ultrasound-guided transbronchial needle
aspiration (EBUS-TBNA) is well-established for lung cancer diagnosis and
staging. Next generation sequencing (NGS) via targeted resequencing allows
simultaneous interrogation for multiple mutations, but has its limitations
S630 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017