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A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study)

Authors
 Yvonne L E Ang  ;  Xiaotian Zhao  ;  Thanyanan Reungwetwattana  ;  Byoung-Chul Cho  ;  Bin-Chi Liao  ;  Rebecca Yeung  ;  Herbert H Loong  ;  Dong-Wan Kim  ;  James Chih-Hsin Yang  ;  Sun Min Lim  ;  Myung-Ju Ahn  ;  Se-Hoon Lee  ;  Thitiporn Suwatanapongched  ;  Kanchaporn Kongchauy  ;  Qiuxiang Ou  ;  Ruoying Yu  ;  Bee Choo Tai  ;  Boon Cher Goh  ;  Tony S K Mok  ;  Ross A Soo 
Citation
 CANCERS, Vol.15(20) : 4999, 2023-10 
Journal Title
CANCERS
Issue Date
2023-10
Keywords
EGFR T790M mutations ; Osimertinib ; circulating tumour DNA ; mechanisms of resistance ; next-generation sequencing
Abstract
Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
Files in This Item:
T202306455.pdf Download
DOI
10.3390/cancers15204999
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lim, Sun Min(임선민)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196857
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