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M.G.O. Fernandes
Author of
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OA08 - Targeted Therapies in Brain Metastases (ID 381)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:D. Ball, B. Perin
- Coordinates: 12/05/2016, 16:00 - 17:30, Schubert 1
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OA08.07 - BRAF-V600E Advanced Lung Adenocarcinoma with Leptomeningeal (LM) Disease Treated with Vemurafenib (ID 4800)
17:05 - 17:15 | Author(s): M.G.O. Fernandes
- Abstract
- Presentation
Background:
BRAF mutations occur in around 3% of non-small cell lung cancers (NSCLC) and V600E accounts for 50%. BRAF V600E is an attractive molecular target for cancer tyrosine kinase treatment, but ideal treatment is still not defined.
Methods:
A case of a patient with BRAF-mutated non–small cell lung cancer (NSCLC) detected by NGS Ion torrent technology who presented with LM disease and was treated with the selective BRAF inhibitor vemurafenib is described.
Results:
58 years old, female, non-smoker, who presented in the emergency department with pericardial effusion. Pericardial fluid cytology confirmed adenocarcinoma TTF1 positive. Multi-organ metastatic disease was diagnosed (bone, lung and thyroid) without EGFR mutation or ALK-EML4 translocation. Four cycles of chemotherapy with pemetrexed and carboplatin were done. She started with refractory headache and vomiting, brain CT and MRI showed no evidence of metastasis, a lumbar puncture confirmed malignant cells in the cerebrospinal fluid. A BRAF V600E was detected by NGS, Ion Torrence PGM technology in the initial tumour sample and in plasma circulating free DNA. An off-label treatment with vemurafenib 960 mg q12hr was offered to the patient, with clinical improvement and radiologic lung stability. At month 2 of treatment, the patient developed respiratory insufficiency with lung infiltrates and Influenza A virus was identified in a nasal swab. Vemurafenib was temporary suspended and re-introduced until 720 mg q12h and maintained until disease progression (large volume pleural effusion with positive cytology), at month 6 of vemurafenib tretament. Third line treatment is being planned.
Conclusion:
The authors highlight the importance of using a multiplex screening strategy to detect targetable mutations in advanced lung cancer patients. The application of next generation sequencing to the tumour and plasma cfDNA allowed the detection of a BRAF-V600E mutation. The improvement of neurologic symptoms and disease control achieved with vemurafenib supports vemurafenib´s efficacy. Care should be taken to the possibility of occurring lung toxicity.
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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-026 - Next-Generation Sequencing for Molecular Diagnosis of Tumour Specimens from Patients with Advanced Lung Adenocarcinoma (ID 5243)
14:30 - 14:30 | Author(s): M.G.O. Fernandes
- Abstract
Background:
Molecular driven therapy of advanced lung adenocarcinoma implies the detection of specific genetic alterations predictive of response to agents targeting specific pathways. Next Generation Sequencing provides simultaneous analysis of hundreds of genes in samples with low DNA quantity with a fast, sensitive technology, even in the presence of low frequency alleles.
Methods:
In this study, the enrichment strategy used was the Ion Ampliseq Colon and Lung panel for tumour biopsies. All amplified products were used to prepare libraries and sequenced using the Ion PGM or S5xl system. The QuantStudio 3D Digital PCR System was used to confirm selected results. 92 patients with advanced lung adenocarcinoma previously tested for EGFR mutation by PCR and for ALK by FISH were included. Significant genetic alterations obtained by NGS are described and compared with those identified by standard techniques.
Results:
NGS was applied to 92 diagnostic samples, corresponding to 63 (68.5%) wild type (WT) patients, 21 (22.8%) with EGFR mutations and 8 (8.7%) with ALK-EML4 translocation. The Ion Torrent PGM confirmed the presence of the EGFR mutation in 20 (95.2%) patients and detected a new case with p.L858R. Among patients classified as WT, 18 had a KRAS mutation, 3 BRAF V600E and 1 STK11; among ALK patients, 2 had a KRAS mutation. Other significant concurrent genetic alterations were found: 2 patients with EGFR and PIK3CA mutations, 2 with EGFR and KRAS and sporadic cases with STK11 and TP53. Only 40 patients remained classified as WT (43,5%).
Conclusion:
NGS is useful for detection of actionable mutations in small tumour biopsies and cytology specimens of lung adenocarcinoma. It allows the identification of more candidates to targeted therapies and the detection of concurrent mutations that can impact prognosis and treatment efficacy.
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P2.03b-027 - Circulating Free DNA (cfDNA) Analysis from Patients with Advanced Lung Adenocarcinoma (ID 5827)
14:30 - 14:30 | Author(s): M.G.O. Fernandes
- Abstract
Background:
Circulating tumour free DNA (cfDNA) is a noninvasive assessment that can be used as an alternative method for gene mutations detection in lung cancer patients and for real time therapeutic monitoring. Detection and quantification of such mutations is difficult and next generation sequencing (NGS) is a promising technology. Concordance between tumour tissue DNA (tDNA) and plasma cfDNA need to be studied and changes in cfDNA correlated with clinical evolution.
Methods:
Ion Ampliseq Colon and Lung panel was used for tissue biopsies and the new Oncomine Lung cfDNA assay for cfDNA samples. All amplified products were used to prepare libraries and sequenced using the Ion PGM or S5xl system. Selected results were confirmed with the QuantStudio 3D Digital PCR. Plasma cfDNA collected at the diagnosis and during disease´s evolution of patients with advanced adenocarcinoma was analysed. cfDNA mutations were compared with tDNA.
Results:
56 patients were included. In the tumour samples 24 activating EGFR mutations, 16 KRAS, 3 BRAF-V600E, 3 TP53, 1 STK11 and 1 PIK3CA were identified. 16 patients were classified as “wild type” (WT). Tumour derived genetic alterations could be identified in cfDNA with allelic frequencies as low as 0.01%. Among the 48 alterations detected on tDNA, 39 (81.3%) were found in cfDNA. Plasma detection failed in 6 EGFR and 3 KRAS. In 3 EGFR patients, concurrent alterations not identified in the tumour were detected: 1 combination with EGFR p.Glu746_Ala750del; 2 with T790M and 1 with ALK p.I1171N. A KRAS mutation was identified in 1 WT patient. cfDNA 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.
