Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
longitudinal variations are being studied and will be updated. Conclusion:
Profiling cfDNA with Ion NSG technology is feasible, allowing the detection
of molecular alterations associated with targeted therapy or valuable
for disease´s monitoring. cfDNA has a good correlation with tumour DNA
alterations, representing a true “liquid biopsy”. The application of NGS to
tumour and plasma samples hold a large spectrum of clinical potentialities.
Keywords: mutations, lung cancer, cfDNA, next generation sequencing
POSTER SESSION 2 – P2.03B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
BIOMARKERS –
TUESDAY, DECEMBER 6, 2016
P2.03B-028 IMPROVED OVERALL SURVIVAL FOLLOWING
IMPLEMENTATION OF NGS IN ROUTINE DIAGNOSTICS OF
ADVANCED LUNG CANCER IN GERMANY: RESULTS OF THE NGM
Anna Kostenko 1 , Sebastian Michels 2 , Jana Fassunke 3 , Lucia Nogova 4 , Sabine
Merkelbach-Bruse 3 , Matthias Scheffler 2 , Vanessa Brandes 2 , Rieke Fischer 2 ,
Andreas Scheel 3 , Florian Kron 1 , Merle Schueller 3 , Frank Ueckeroth 3 , Reinhard
Buettner 3 , Jürgen Wolf 5
1 Department I of Internal Medicine and Center of Integrated Oncology Cologne
Bonn, University Hospital of Cologne, Cologne/Germany, 2 Department I, Lung
Cancer Group Cologne, University Hospital of Cologne, Cologne/Germany,
3 Institute of Pathology, University Hospital of Cologne, Cologne/Germany, 4 Lung
Cancer Group Cologne, University Hospital of Cologne, Cologne/Germany, 5 Lung
Cancer Group Cologne, Department I of Internal Medicine, University Hospital of
Cologne, Cologne/Germany
Background: Broad implementation of molecular diagnostics and
personalized cancer care is hampered by insufficient molecular screening,
missing reimbursement for comprehensive molecular testing and lack of
access to appropriate drugs. The Network Genomic Medicine (NGM) Lung
Cancer is a health care provider network offering comprehensive next
generation sequencing (NGS)-based multiplex genotyping on a central
diagnostics platform in Cologne for all inoperable lung cancer patients
(pts) in Germany. Methods: The NGS panel used in NGM consists of 14
genes and 102 amplicons to cover potentially targetable aberrations.
Mutation analyses were run on an Illumina (MySeq) platform, while FISH
analyses were performed separately. In 2015, we have started the second
outcome evaluation for all NGM pts who had received NGS-based molecular
diagnostics. In particular, we have focused on molecular subgroups of EGFR,
ALK, BRAF-V600E, HER2 and ROS1 positive pts and especially on NGM pts
treated in clinical trials. Results: From 2013-2015 6210 lung cancer pts (n=4244
non-squamous NSCLC) were genotyped. Preliminary data show the overall
survival (OS) of 934 NSCLC pts including of 110 NSCLC pts treated in clinical
trials. For 108 EGFR+ pts, the OS of clinical trials pts treated with so called 3rd
generation EGFR-TKIs was 55 months (n=25) vs 22 months in control group
(n=83) (p=0,002; mean OS: 29 months; 95%CI: 36-83 months). For 85 ALK+
pts, the OS of pts treated in clinical trials was 35 months (n=19) compared
to OS of 23 months for 45 pts treated with one ALK inhibitor and 8 months
for 19 pts treated with no ALK inhibitors (P 99.9999%) (PLoS One, 10(10), 2015).
Results: 254 Guardant360 tests were completed in 250 pts (144/F:106/M);
histology: adenocarcinoma(200), squamous(7), sarcomatoid(5), small cell(4)
and others(34). Rationale for blood tests: addition to tissue analysis(39%),
alternative to tissue biopsy(25%), treatment evaluation/resistant(18%),
insufficient tissue(11%), no documentation(7%). Based on Guardant360
results, 77 pt samples (30.3%) demonstrated targetable alterations with
FDA-approved agents; concordance with at least 1 genomic alteration
(targetable with FDA-approved agent) from paired tissue analysis in 21pts;
and in another 29 pts, new genomic alterations provided evaluation for
potential change in therapies pts: EGFR T790M(n=21), EML4-ALK fusion(n=4),
MET Exon 14 Skipping (3), EGFR ex19del(n=2), EGFR L858R(n=2), other
targets(n=6). Significantly, detection of EGFR T790M in cfDNA lead to change
in therapy with osimertinib 19 cases and eligibility to clinical studies in 2
cases with alterations in KIF5B-RET and NOTCH1,respectively. Additional
clinical outcomes are pending and will be updated. Conclusion: Molecular
testing of cfDNA is a simple, minimally invasive test. It has utility to obviate
a repeat invasive tissue biopsy when the initial tissue sample is not available
or inadequate for molecular analysis. It is particularly useful in the long-term
management of patients at progression for detection of emergent resistanceassociated
molecular alterations; such as EGFR T790M.
Keywords: lung cancer, cfDNA, ctDNA, molecular alterations
S498 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017