Molecular Analysis of Plasma From Patients With ROS1-Positive NSCLC

Slides:

Advertisements

Similar presentations

Choroidal Metastases Responsive to Crizotinib Therapy in a Lung Adenocarcinoma Patient with ALK 2p23 Fusion Identified by ALK Immunohistochemistry Yan.

Advertisements

CtDNA NGS testing identified a high-level MET amplification (copy number of 53.6 in circulation) (Figure 1A). The test was repeated on a second tube of.

Frances A Shepherd, MD, Rafael Rosell, MD Journal of Thoracic Oncology

A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing–Based Circulating Tumor DNA Profiling Exhibits Excellent Response.

Acquired Resistance to Crizotinib from a Mutation in CD74-ROS1 Mark M

Droplet Digital PCR for Absolute Quantification of EML4-ALK Gene Rearrangement in Lung Adenocarcinoma Qiushi Wang, Xin Yang, Yong He, Qiang Ma, Li Lin,

Receptor Tyrosine Kinase Fusions and BRAF Kinase Fusions are Rare but Actionable Resistance Mechanisms to EGFR Tyrosine Kinase Inhibitors Alexa B. Schrock,

Chia-Lin Hsu, MD, Kuan-Yu Chen, MD, PhD Journal of Thoracic Oncology

Rafal Dziadziuszko, MD, PhD, Anh T

T790M EGFR Mutation Detection in Cerebrospinal Fluid and Response to Osimertinib in a Lung Cancer Patient with Meningeal Carcinomatosis Hugo Gortais,

A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing–Based Circulating Tumor DNA Profiling Exhibits Excellent Response.

Recent Advances in Targeting ROS1 in Lung Cancer

Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic.

Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations

Cases of ALK-Rearranged Lung Cancer with 5-Year Progression-Free Survival with Crizotinib as Initial Precision Therapy Deepa Rangachari, MD, Xiuning.

Jessica J. Lin, MD, Lauren L. Ritterhouse, MD, PhD, Siraj M

Dramatic Response to Combination Erlotinib and Crizotinib in a Patient with Advanced, EGFR-Mutant Lung Cancer Harboring De Novo MET Amplification Justin.

Detection of Discrepant Driver Mutations in a Patient with Two Synchronous Primary Non–Small Cell Lung Cancers (NSCLCs) with Liquid Biopsy Sotirios Lakis,

FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma Sandra Salvi, PhD, Serena Varesano, PhD, Simona Boccardo, PhD, Jean Louis.

Clinicopathologic Analysis of ROS1-Rearranged Non–Small-Cell Lung Cancer and Proposal of a Diagnostic Algorithm Heounjeong Go, MD, PhD, Dong-Wan Kim,

A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib Trish Thorne-Nuzzo, BS, Crystal.

Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Third- Generation EGFR Tyrosine Kinase Inhibitor Alessandra Bearz, MD, Elisa.

T790M EGFR Mutation Detection in Cerebrospinal Fluid and Response to Osimertinib in a Lung Cancer Patient with Meningeal Carcinomatosis Hugo Gortais,

The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC Si-Yang Liu, MD, Lan-Ying Gou, MD, An-Na Li, MD, Na-Na Lou, MMed, Hong-Fei.

Susan C. Scott, MD, Nathan A. Pennell, MD, PhD

Megan B. Barnet, BS, M. B. B. S. , Sandra O’Toole, PhD, Lisa G

Victoria Wang, MD, PhD, Trever Bivona, MD, PhD

A Novel EGFRC797 Variant Detected in a Pleural Biopsy Specimen from an Osimertinib-Treated Patient Using a Comprehensive Hybrid Capture–Based Next- Generation.

Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Non–Small Cell Lung Cancer Alexa B. Schrock, PhD, Allison.

Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients Clotilde Descarpentries, PharmD, Frédéric Leprêtre, PhD, Fabienne.

Meghan Campo, MD, David Gerber, MD, Justin F. Gainor, MD, Rebecca S

Clinical Outcome of ALK-Positive Non–Small Cell Lung Cancer (NSCLC) Patients with De Novo EGFR or KRAS Co-Mutations Receiving Tyrosine Kinase Inhibitors.

Multiple Acquired Resistance Mutations of the ALK Tyrosine Kinase Domain after Sequential Use of ALK Inhibitors Hsin-Yi Wang, MD Journal of Thoracic.

Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung Adenocarcinoma

Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping

Comprehensive Hybrid Capture–Based Next-Generation Sequencing Identifies a Double ALK Gene Fusion in a Patient Previously Identified to Be False-Negative.

The Central Nervous System as a Sanctuary Site in ALK-Positive Non–Small-Cell Lung Cancer Justin F. Gainor, MD, Sai-Hong Ignatius Ou, MD, PhD, Jennifer.

A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib Trish Thorne-Nuzzo, BS, Crystal.

Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment

A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib Helena A. Yu,

Reliability Assurance of Detection of EML4-ALK Rearrangement in Non–Small Cell Lung Cancer: The Results of Proficiency Testing in China Yulong Li, MD,

Emergence of Preexisting MET Y1230C Mutation as a Resistance Mechanism to Crizotinib in NSCLC with MET Exon 14 Skipping Sai-Hong Ignatius Ou, MD, PhD,

Recent Advances in Targeting ROS1 in Lung Cancer

Strategies to Improve Outcomes of Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Review of the Literature Caicun Zhou, MD, PhD, Luan Di Yao, MD

Comprehensive Analysis of the Discordance of EGFR Mutation Status between Tumor Tissues and Matched Circulating Tumor DNA in Advanced Non–Small Cell Lung.

Identification of a Novel HIP1-ALK Fusion Variant in Non–Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged.

Choroidal Metastases Responsive to Crizotinib Therapy in a Lung Adenocarcinoma Patient with ALK 2p23 Fusion Identified by ALK Immunohistochemistry Yan.

Response to Crizotinib Observed in Lung Adenocarcinoma with MET Copy Number Gain but without a High-Level MET/CEP7 Ratio, MET Overexpression, or Exon.

Erratum Journal of Thoracic Oncology

A Different Method in Diagnosis of Multiple Primary Lung Cancer

Arnaud Uguen, MD, PhD Journal of Thoracic Oncology

A Case of ALK-Rearranged Adenocarcinoma with Small Cell Carcinoma-Like Transformation and Resistance to Crizotinib Yoon Jin Cha, MD, PhD, Byoung Chul.

Jessica J. Lin, MD, Ginger Y

Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable.

Daniel B. Costa, MD, PhD, Susumu Kobayashi, MD, PhD

Compound Uncommon EGFR Mutations in a Patient with Advanced NSCLC and Durable Response to Sequential EGFR Targeted Therapies Mary Linton B Peters, MD,

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non– Small Cell Lung Cancer Emily Castellanos, MD, Emily Feld, MD, Leora.

Concomitant Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion in a Patient with Multifocal Lung Adenocarcinomas Jun Fan, MD Journal of Thoracic.

Clinical Implications of Variant ALK FISH Rearrangement Patterns

Highly Sensitive Detection of EGFR T790M Mutation in Pre-TKI Specimens of EGFR- Mutated NSCLC: In Cis, In Trans, or a Different Clone? Alvaro Leone, BSc.D

Daniel B. Costa, MD, PhD, Susan E. Jorge, PhD, Jason P

Impressive Response to Tyrosine Kinase Inhibitors in a Patient with Respiratory Failure for EGFR-Mutated Metastatic Lung Cancer Elena Bolzacchini, MD,

Acquired Mechanism of Crizotinib Resistance in NSCLC with MET Exon 14 Skipping Wei Jin, MD, Benjie Shan, MD, Hu Liu, PhD, Shoubing Zhou, PhD, Wenjuan.

MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels

Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer Relapsing.

Clinicopathologic Features of NSCLC Diagnosed During Pregnancy or the Peripartum Period in the Era of Molecular Genotyping Ibiayi Dagogo-Jack, MD, Justin.

Waxing and Waning of MET Amplification in EGFR-Mutated NSCLC in Response to the Presence and Absence of Erlotinib Selection Pressure Joel P. Womack,

ALK Gene Rearrangements: A New Therapeutic Target in a Molecularly Defined Subset of Non-small Cell Lung Cancer Benjamin Solomon, MBBS, PhD, Marileila.

Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung Adenocarcinoma

The Current Role of Whole Brain Radiation Therapy in Non–Small Cell Lung Cancer Patients Gokoulakrichenane Loganadane, MD, Lizza Hendriks, MD, PhD, Cécile.

Presentation transcript:

Molecular Analysis of Plasma From Patients With ROS1-Positive NSCLC Ibiayi Dagogo-Jack, MD, Marguerite Rooney, BS, Rebecca J. Nagy, MS, Jessica J. Lin, MD, Emily Chin, BS, Lorin A. Ferris, MS, Jennifer Ackil, NP, Jochen K. Lennerz, MD, Richard B. Lanman, MD, Justin F. Gainor, MD, Alice T. Shaw, MD, PhD Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2019.01.009 Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Study population. The schematic represents the population of patients studied in this analysis. Plasma specimens are indicated in blue. Tissue specimens are identified by green rectangles. Yellow boxes refer to overlap between two methods. NGS, next-generation sequencing; FISH, fluorescence in-situ hybridization; TKI, tyrosine kinase inhibitor; MGH, Massachusetts General Hospital; ctDNA, circulating tumor DNA Journal of Thoracic Oncology DOI: (10.1016/j.jtho.2019.01.009) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Spectrum of ROS1 fusion partners. The pie charts represent the relative prevalence of distinct fusion partners in plasma (A) and tissue (B). Journal of Thoracic Oncology DOI: (10.1016/j.jtho.2019.01.009) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Landscape of genetic alterations in crizotinib-resistant plasma specimens. The grid depicts genetic alterations detected in plasma collected from patients with ROS1-positive lung cancer at relapse on crizotinib. In some cases, multiple genetic alterations involving a single gene were identified but this is not captured in the heatmap. Apart from CDKN2A which includes copy number changes, all other genetic alterations were single nucleotide variants. Journal of Thoracic Oncology DOI: (10.1016/j.jtho.2019.01.009) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Spatial heterogeneity captured through plasma genotyping. The figures illustrate the disease course of a patient with ROS1-positive NSCLC sequentially treated with crizotinib followed by crizotinib combined with chemotherapy. The patient did not have liver metastases at diagnosis (A) but developed new liver lesions (B) after 3 months on crizotinib at which time only plasma detected ROS1 G2032R. At subsequent progression on combination therapy, G2032R was detected in pleural fluid (pleural fluid is absent pre-treatment in C and present at relapse in D) and plasma. Journal of Thoracic Oncology DOI: (10.1016/j.jtho.2019.01.009) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions