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F. Ueckeroth
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-028 - Improved Overall Survival Following Implementation of NGS in Routine Diagnostics of Advanced Lung Cancer in Germany: Results of the NGM (ID 5304)
14:30 - 14:30 | Author(s): F. Ueckeroth
- Abstract
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 3[rd] 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<0,0001; mean OS: 22 months; 95%CI: 22-33 months).
Conclusion:
While the first NGM evaluation in 2013 already showed a survival benefit of 2 years in EGFR-TKI treated EGFR+ pts compared to chemotherapy, our current evaluation in pts treated with 3[rd] generation EGFR-TKIs after acquired resistance to 1[st] gen. EGFR-TKIs shows the significant increasing of the OS. Similarly, we show a significant longer OS for ALK+ pts treated with 2 ALK inhibitors compared to treatment with one or no ALK inhibitor. Further results of this ongoing NGM evaluation will be provided.
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P2.03b-036 - Analysis of Potentially Targetable Mutations in 821 Patients with Squamouscell Lung Cancer Undergoing Routine NGS-Based Molecular Diagnostics (ID 5939)
14:30 - 14:30 | Author(s): F. Ueckeroth
- Abstract
Background:
Molecular multiplex diagnostics is increasingly integrated now in routine diagnostics of lung adenocarcinoma (LAD). Although targetable aberrations are predominantly found in LAD, they have also been reported in squamouscell lung carcinoma (SQLC). We here present results of routine molecular multiplex diagnostics of advanced stage SQLC obtained within the German Network Genomic Medicine (NGM) and compare them with results reported previously in early stage SQLC in The Cancer Genome Atlas (TCGA) LUSC cohort.
Methods:
Tumor biopsies of 821 patients consecutively diagnosed within NGM were analyzed with next-generation parallel sequencing (NGS). The panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For NGM patients, therapy and outcome are also reported..
Results:
In addition to the expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort included also activating targetable mutations (i. e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load will be presented.
Conclusion:
Our data give an overview on the presence and clinical characteristics of targetable mutations in advanced SQLC and show, that such mutations occur in a substantial amount of patients. Thus, molecular multiplex diagnostics might be indicated also in SQLC in order to use all therapeutic options available in these patients.
