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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)

 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 
 CANCERS, Vol.15(20) : 4999, 2023-10 
Journal Title
Issue Date
EGFR T790M mutations ; Osimertinib ; circulating tumour DNA ; mechanisms of resistance ; next-generation sequencing
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.
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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
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