Abstract
Introduction: In patients with oncogene-addicted NSCLC and isolated central nervous system progression (iCNS), tissue biopsy is challenging, and the clinical utility of plasma liquid biopsy (i.e., circulating tumor DNA [ctDNA]) is unknown.
Methods: Patients with advanced NSCLC with known baseline genomic alteration (GA) (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, PIK3CA, STK11, TP53) on tissue were divided into three groups on the basis of their disease progression pattern: iCNS, extra-CNS only (noCNS), or both (cCNS). All patients with available plasma ctDNA were included and were analyzed by next-generation sequencing InVisionFirst-Lung. ctDNA was considered positive if at least one GA was detected. Cell-free tumor DNA was analyzed in cerebrospinal fluid when available.
Results: Out of 517 patients screened, 247 were included: 54 had iCNS, 99 had noCNS, and 94 had cCNS progressive disease (64, 128, and 110 ctDNA samples, respectively). CtDNA was positive in 52% iCNS versus 84% in noCNS and 92% in cCNS (p <0.00001), with lower detection of driver (37% versus 77% and 73%, respectively) and resistance alterations (6% versus 45% and 44%). Patients with iCNS and positive ctDNA were more at risk of extra-CNS progression (32% versus 7%, p = 0.026). In 12 patients with iCNS, ctDNA was positive in six (50%) plasma and in 10 (83%) paired cerebrospinal fluid (p = 0.193).
Conclusions: Although tagged amplicon-based nex-tgeneration sequencing has high detection rates of GA in plasma ctDNA in patients with NSCLC with extra-CNS disease, detection rate of GAs (52%) is lower in the subset of patients with iCNS disease. Complementary tests such as cerebrospinal fluid cell-free DNA may be useful. Further evidence would be beneficial to understand the genomic landscape in patients with NSCLC and iCNS. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 383-391 |
| Number of pages | 9 |
| Journal | Journal of Thoracic Oncology |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2020 |
Keywords
- Liquid biopsy
- ctDNA
- NSCLC
- Brain
- Leptomeningeal
- CELL LUNG-CANCER
- TYROSINE KINASE INHIBITORS
- CEREBROSPINAL-FLUID
- LEPTOMENINGEAL METASTASIS
- CRIZOTINIB
- PLASMA
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In: Journal of Thoracic Oncology, Vol. 15, No. 3, 03.2020, p. 383-391.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Circulating Tumor DNA Analysis for Patients with Oncogene-Addicted NSCLC With Isolated Central Nervous System Progression
AU - Aldea, Mihaela
AU - Hendriks, Lizza
AU - Mezquita, Laura
AU - Jovelet, Cecile
AU - Planchard, David
AU - Auclin, Edouard
AU - Remon, Jordi
AU - Howarth, Karen
AU - Benitez, Jose Carlos
AU - Gazzah, Anas
AU - Lavaud, Pernelle
AU - Naltet, Charles
AU - Lacroix, Ludovic
AU - de Kievit, Frank
AU - Morris, Clive
AU - Green, Emma
AU - Ngo-Camus, Maud
AU - Rouleau, Etienne
AU - Massard, Christophe
AU - Caramella, Caroline
AU - Friboulet, Luc
AU - Besse, Benjamin
N1 - Funding Information: Disclosure: Dr. Hendriks has received research funding from Roche , Boehringer Ingelheim , and AstraZeneca (all institution); has served on the advisory board for Boehringer, BMS, Lilly, and Roche (all institution, BMS also self); has received travel/conference reimbursement from Roche and BMS (self); participated in mentorship program with key opinion leaders that was funded by AstraZeneca ; and has received fees for educational webinars from Quadia (self). Dr. Mezquita has provided consulting and advisory role for Roche Diagnostics; provided lectures and educational activities for Bristol-Myers Squibb, Tecnofarma, Roche, and AstraZeneca; and has received travel, accommodations, and expenses from Chugai. Dr. Planchard has provided consulting, advisory role, or lectures for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; has performed clinical trials research for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and has received travel, accommodations, and expenses from AstraZeneca, Roche, Novartis, prIME Oncology, and Pfizer. Dr. Remon has provided advisory services for MSD, BMS, AstraZeneca, and Boehringer; is a speaker for Pfizer; has received travel expenses from OSE Immunotherapeutics, BMS, AstraZeneca, and Roche; and has received personal fees from OSE Immunotherapeutics. Dr. Howarth is an employee and shareholder of Inivata. Dr. Gazzah has received travel, accommodation, and congress registration expenses from Boehringer Ingelheim, Novartis, Pfizer, and Roche; has provided consultant/expert role for Novartis; is a principal/subinvestigator of clinical trials for Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech Inc., Gilead Sciences Inc., Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine Inc., Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servier, Janssen, Kura Oncology, Kyowa Kirin Pharm, Lilly, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec Gmbh, Roche, Sanofi-Aventis, Sierra Oncology, Taiho Pharma, Tesaro Inc., Tioma Therapeutics Inc., and Xencor; has received research grants from AstraZeneca , BMS , Boehringer Ingelheim , Janssen Cilag, Merck , Novartis , Pfizer , Roche , and Sanofi ; and reports nonfinancial support (drug supplied) from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, and Roche. Dr. Lavaud reports travel and accommodation from Astellas -Pharma, Astra Zeneca , Ipsen, Janssen Oncology, and Mundi Pharma. Dr. Lacroix has provided consulting, advisory role, or lectures for Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Ca Bayer Healthcarer, Illumina, Genomic Health, Myriad, Novartis, Pfizer, Roche, Siemens, Thermofisher, and VelaDx. Drs. de Kievit, Morris, and Green are employees and shareholders of Inivata. Dr. Rouleau served on the Board for BMS, AstraZeneca, and Roche. Dr. Massard has received consultant/advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, and Orion; and is the principal/subinvestigator of clinical trials for Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedicine, Incyte, InnatePharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, LytixBiopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, NektarTherapeutics, Novartis, Octimet, Oncoethix, OncopeptidesAB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, and Xencor. Dr. Besse reports sponsored research at Gustave Roussy Cancer Center from Abbvie , Amgen , AstraZeneca , Biogen , Blueprint Medicines, BMS , Celgene , Eli Lilly , GSK , Ignyta , IPSEN, Merck KGaA , MSD , Nektar, Onxeo, Pfizer , Pharma Mar , Sanofi , Spectrum Pharmaceuticals , Takeda, and Tiziana Pharma; and is an investigator or co-investigator of trials for Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, Abbvie, Loxo Oncology, AstraZeneca, and Blueprint Medicines. The remaining authors declare no conflict of interest. Funding Information: Disclosure: Dr. Hendriks has received research funding from Roche, Boehringer Ingelheim, and AstraZeneca (all institution); has served on the advisory board for Boehringer, BMS, Lilly, and Roche (all institution, BMS also self); has received travel/conference reimbursement from Roche and BMS (self); participated in mentorship program with key opinion leaders that was funded by AstraZeneca; and has received fees for educational webinars from Quadia (self). Dr. Mezquita has provided consulting and advisory role for Roche Diagnostics; provided lectures and educational activities for Bristol-Myers Squibb, Tecnofarma, Roche, and AstraZeneca; and has received travel, accommodations, and expenses from Chugai. Dr. Planchard has provided consulting, advisory role, or lectures for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; has performed clinical trials research for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and has received travel, accommodations, and expenses from AstraZeneca, Roche, Novartis, prIME Oncology, and Pfizer. Dr. Remon has provided advisory services for MSD, BMS, AstraZeneca, and Boehringer; is a speaker for Pfizer; has received travel expenses from OSE Immunotherapeutics, BMS, AstraZeneca, and Roche; and has received personal fees from OSE Immunotherapeutics. Dr. Howarth is an employee and shareholder of Inivata. Dr. Gazzah has received travel, accommodation, and congress registration expenses from Boehringer Ingelheim, Novartis, Pfizer, and Roche; has provided consultant/expert role for Novartis; is a principal/subinvestigator of clinical trials for Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech Inc., Gilead Sciences Inc., Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine Inc., Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servier, Janssen, Kura Oncology, Kyowa Kirin Pharm, Lilly, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec Gmbh, Roche, Sanofi-Aventis, Sierra Oncology, Taiho Pharma, Tesaro Inc., Tioma Therapeutics Inc., and Xencor; has received research grants from AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, and Sanofi; and reports nonfinancial support (drug supplied) from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, and Roche. Dr. Lavaud reports travel and accommodation from Astellas-Pharma, Astra Zeneca, Ipsen, Janssen Oncology, and Mundi Pharma. Dr. Lacroix has provided consulting, advisory role, or lectures for Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Ca Bayer Healthcarer, Illumina, Genomic Health, Myriad, Novartis, Pfizer, Roche, Siemens, Thermofisher, and VelaDx. Drs. de Kievit, Morris, and Green are employees and shareholders of Inivata. Dr. Rouleau served on the Board for BMS, AstraZeneca, and Roche. Dr. Massard has received consultant/advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, and Orion; and is the principal/subinvestigator of clinical trials for Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedicine, Incyte, InnatePharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, LytixBiopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, NektarTherapeutics, Novartis, Octimet, Oncoethix, OncopeptidesAB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, and Xencor. Dr. Besse reports sponsored research at Gustave Roussy Cancer Center from Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, and Tiziana Pharma; and is an investigator or co-investigator of trials for Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, Abbvie, Loxo Oncology, AstraZeneca, and Blueprint Medicines. The remaining authors declare no conflict of interest. Publisher Copyright: © 2019 International Association for the Study of Lung Cancer
PY - 2020/3
Y1 - 2020/3
N2 - Introduction: In patients with oncogene-addicted NSCLC and isolated central nervous system progression (iCNS), tissue biopsy is challenging, and the clinical utility of plasma liquid biopsy (i.e., circulating tumor DNA [ctDNA]) is unknown.Methods: Patients with advanced NSCLC with known baseline genomic alteration (GA) (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, PIK3CA, STK11, TP53) on tissue were divided into three groups on the basis of their disease progression pattern: iCNS, extra-CNS only (noCNS), or both (cCNS). All patients with available plasma ctDNA were included and were analyzed by next-generation sequencing InVisionFirst-Lung. ctDNA was considered positive if at least one GA was detected. Cell-free tumor DNA was analyzed in cerebrospinal fluid when available.Results: Out of 517 patients screened, 247 were included: 54 had iCNS, 99 had noCNS, and 94 had cCNS progressive disease (64, 128, and 110 ctDNA samples, respectively). CtDNA was positive in 52% iCNS versus 84% in noCNS and 92% in cCNS (p <0.00001), with lower detection of driver (37% versus 77% and 73%, respectively) and resistance alterations (6% versus 45% and 44%). Patients with iCNS and positive ctDNA were more at risk of extra-CNS progression (32% versus 7%, p = 0.026). In 12 patients with iCNS, ctDNA was positive in six (50%) plasma and in 10 (83%) paired cerebrospinal fluid (p = 0.193).Conclusions: Although tagged amplicon-based nex-tgeneration sequencing has high detection rates of GA in plasma ctDNA in patients with NSCLC with extra-CNS disease, detection rate of GAs (52%) is lower in the subset of patients with iCNS disease. Complementary tests such as cerebrospinal fluid cell-free DNA may be useful. Further evidence would be beneficial to understand the genomic landscape in patients with NSCLC and iCNS. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
AB - Introduction: In patients with oncogene-addicted NSCLC and isolated central nervous system progression (iCNS), tissue biopsy is challenging, and the clinical utility of plasma liquid biopsy (i.e., circulating tumor DNA [ctDNA]) is unknown.Methods: Patients with advanced NSCLC with known baseline genomic alteration (GA) (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, PIK3CA, STK11, TP53) on tissue were divided into three groups on the basis of their disease progression pattern: iCNS, extra-CNS only (noCNS), or both (cCNS). All patients with available plasma ctDNA were included and were analyzed by next-generation sequencing InVisionFirst-Lung. ctDNA was considered positive if at least one GA was detected. Cell-free tumor DNA was analyzed in cerebrospinal fluid when available.Results: Out of 517 patients screened, 247 were included: 54 had iCNS, 99 had noCNS, and 94 had cCNS progressive disease (64, 128, and 110 ctDNA samples, respectively). CtDNA was positive in 52% iCNS versus 84% in noCNS and 92% in cCNS (p <0.00001), with lower detection of driver (37% versus 77% and 73%, respectively) and resistance alterations (6% versus 45% and 44%). Patients with iCNS and positive ctDNA were more at risk of extra-CNS progression (32% versus 7%, p = 0.026). In 12 patients with iCNS, ctDNA was positive in six (50%) plasma and in 10 (83%) paired cerebrospinal fluid (p = 0.193).Conclusions: Although tagged amplicon-based nex-tgeneration sequencing has high detection rates of GA in plasma ctDNA in patients with NSCLC with extra-CNS disease, detection rate of GAs (52%) is lower in the subset of patients with iCNS disease. Complementary tests such as cerebrospinal fluid cell-free DNA may be useful. Further evidence would be beneficial to understand the genomic landscape in patients with NSCLC and iCNS. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
KW - Liquid biopsy
KW - ctDNA
KW - NSCLC
KW - Brain
KW - Leptomeningeal
KW - CELL LUNG-CANCER
KW - TYROSINE KINASE INHIBITORS
KW - CEREBROSPINAL-FLUID
KW - LEPTOMENINGEAL METASTASIS
KW - CRIZOTINIB
KW - PLASMA
U2 - 10.1016/j.jtho.2019.11.024
DO - 10.1016/j.jtho.2019.11.024
M3 - Article
C2 - 31843682
SN - 1556-0864
VL - 15
SP - 383
EP - 391
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 3
ER -