Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC
Introduction: Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with NSCLC with acquired EGFR T790M mutations. We assessed changes in serial plasma cell-free...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-01-01
|
| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364320301454 |
| _version_ | 1819159897920503808 |
|---|---|
| author | Bin-Chi Liao, MD Wei-Hsun Hsu, MD Jih-Hsiang Lee, MD Ching-Yao Yang, MD, PhD Tzu-Hsiu Tsai, MD, PhD Wei-Yu Liao, MD, PhD Chao-Chi Ho, MD, PhD Chia-Chi Lin, MD, PhD Jin-Yuan Shih, MD, PhD Chong-Jen Yu, MD, PhD Ross A. Soo, M.B.B.S. James Chih-Hsin Yang, MD, PhD |
| author_facet | Bin-Chi Liao, MD Wei-Hsun Hsu, MD Jih-Hsiang Lee, MD Ching-Yao Yang, MD, PhD Tzu-Hsiu Tsai, MD, PhD Wei-Yu Liao, MD, PhD Chao-Chi Ho, MD, PhD Chia-Chi Lin, MD, PhD Jin-Yuan Shih, MD, PhD Chong-Jen Yu, MD, PhD Ross A. Soo, M.B.B.S. James Chih-Hsin Yang, MD, PhD |
| author_sort | Bin-Chi Liao, MD |
| collection | DOAJ |
| description | Introduction: Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with NSCLC with acquired EGFR T790M mutations. We assessed changes in serial plasma cell-free circulating tumor DNA (ctDNA) genomic alterations to predict osimertinib efficacy. Methods: We prospectively collected plasma from patients having EGFR-mutated advanced NSCLC previously treated with EGFR tyrosine kinase inhibitor therapy and with acquired EGFR T790M mutation detected by standard methods. Plasma samples were collected before starting osimertinib treatment, 4 weeks after osimertinib treatment, and on progression. ctDNA was analyzed using the Guardant360 assay. Results: A total of 15 eligible patients received osimertinib. Before starting treatment, EGFR-activating mutations were detected in the ctDNA of all patients, and EGFR T790M was detected in 93% of the cases. Osimertinib treatment was associated with an objective response rate of 53% and a median progression-free survival of 7.3 months. A total of 12 of the 15 patients had undetectable plasma T790M and decreased activating mutation allelic frequency (AF) at week 4. None of the 12 patients had disease progression within 16 weeks. For the remaining three patients, with detectable plasma T790M (n = 2) or increased activating mutation AF (n = 1) at week 4, two had progressive disease within 16 weeks (p = 0.03). Conclusions: In patients with EGFR-mutated advanced NSCLC, persistent EGFR T790M or increasing activating mutation AF as detected in ctDNA 4 weeks after the start of osimertinib treatment may predict disease progression within 16 weeks. |
| first_indexed | 2024-12-22T16:47:52Z |
| format | Article |
| id | doaj.art-59fd29f803354bd7b569000548323489 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-12-22T16:47:52Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-59fd29f803354bd7b5690005483234892022-12-21T18:19:41ZengElsevierJTO Clinical and Research Reports2666-36432021-01-0121100099Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLCBin-Chi Liao, MD0Wei-Hsun Hsu, MD1Jih-Hsiang Lee, MD2Ching-Yao Yang, MD, PhD3Tzu-Hsiu Tsai, MD, PhD4Wei-Yu Liao, MD, PhD5Chao-Chi Ho, MD, PhD6Chia-Chi Lin, MD, PhD7Jin-Yuan Shih, MD, PhD8Chong-Jen Yu, MD, PhD9Ross A. Soo, M.B.B.S.10James Chih-Hsin Yang, MD, PhD11Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of ChinaDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of ChinaDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaDepartment of Hematology-Oncology, National University Hospital, Singapore; Department of Hematology-Oncology, National University Cancer Institute, SingaporeDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; Corresponding author. Address for correspondence: James Chih-Hsin Yang, MD, PhD, Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 100, Taiwan, Republic of China.Introduction: Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with NSCLC with acquired EGFR T790M mutations. We assessed changes in serial plasma cell-free circulating tumor DNA (ctDNA) genomic alterations to predict osimertinib efficacy. Methods: We prospectively collected plasma from patients having EGFR-mutated advanced NSCLC previously treated with EGFR tyrosine kinase inhibitor therapy and with acquired EGFR T790M mutation detected by standard methods. Plasma samples were collected before starting osimertinib treatment, 4 weeks after osimertinib treatment, and on progression. ctDNA was analyzed using the Guardant360 assay. Results: A total of 15 eligible patients received osimertinib. Before starting treatment, EGFR-activating mutations were detected in the ctDNA of all patients, and EGFR T790M was detected in 93% of the cases. Osimertinib treatment was associated with an objective response rate of 53% and a median progression-free survival of 7.3 months. A total of 12 of the 15 patients had undetectable plasma T790M and decreased activating mutation allelic frequency (AF) at week 4. None of the 12 patients had disease progression within 16 weeks. For the remaining three patients, with detectable plasma T790M (n = 2) or increased activating mutation AF (n = 1) at week 4, two had progressive disease within 16 weeks (p = 0.03). Conclusions: In patients with EGFR-mutated advanced NSCLC, persistent EGFR T790M or increasing activating mutation AF as detected in ctDNA 4 weeks after the start of osimertinib treatment may predict disease progression within 16 weeks.http://www.sciencedirect.com/science/article/pii/S2666364320301454Non–small cell lung cancerEGFR mutationsctDNAOsimertinibOutcome prediction |
| spellingShingle | Bin-Chi Liao, MD Wei-Hsun Hsu, MD Jih-Hsiang Lee, MD Ching-Yao Yang, MD, PhD Tzu-Hsiu Tsai, MD, PhD Wei-Yu Liao, MD, PhD Chao-Chi Ho, MD, PhD Chia-Chi Lin, MD, PhD Jin-Yuan Shih, MD, PhD Chong-Jen Yu, MD, PhD Ross A. Soo, M.B.B.S. James Chih-Hsin Yang, MD, PhD Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC JTO Clinical and Research Reports Non–small cell lung cancer EGFR mutations ctDNA Osimertinib Outcome prediction |
| title | Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC |
| title_full | Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC |
| title_fullStr | Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC |
| title_full_unstemmed | Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC |
| title_short | Serial Plasma Cell-Free Circulating Tumor DNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in EGFR T790M–Positive NSCLC |
| title_sort | serial plasma cell free circulating tumor dna tests identify genomic alterations for early prediction of osimertinib treatment outcome in egfr t790m positive nsclc |
| topic | Non–small cell lung cancer EGFR mutations ctDNA Osimertinib Outcome prediction |
| url | http://www.sciencedirect.com/science/article/pii/S2666364320301454 |
| work_keys_str_mv | AT binchiliaomd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT weihsunhsumd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT jihhsiangleemd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT chingyaoyangmdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT tzuhsiutsaimdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT weiyuliaomdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT chaochihomdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT chiachilinmdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT jinyuanshihmdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT chongjenyumdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT rossasoombbs serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc AT jameschihhsinyangmdphd serialplasmacellfreecirculatingtumordnatestsidentifygenomicalterationsforearlypredictionofosimertinibtreatmentoutcomeinegfrt790mpositivensclc |