https://scholars.lib.ntu.edu.tw/handle/123456789/637201
標題: | 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) | 作者: | Ang, Yvonne L E Zhao, Xiaotian Reungwetwattana, Thanyanan Cho, Byoung-Chul BIN-CHI LIAO Yeung, Rebecca Loong, Herbert H Kim, Dong-Wan CHIH-HSIN YANG Lim, Sun Min Ahn, Myung-Ju Lee, Se-Hoon Suwatanapongched, Thitiporn Kongchauy, Kanchaporn Ou, Qiuxiang Yu, Ruoying Tai, Bee Choo Goh, Boon Cher Mok, Tony S K Soo, Ross A |
關鍵字: | EGFR T790M mutations; Osimertinib; circulating tumour DNA; mechanisms of resistance; next-generation sequencing | 公開日期: | 16-十月-2023 | 卷: | 15 | 期: | 20 | 來源出版物: | Cancers | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637201 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers15204999 |
顯示於: | 醫學院附設癌醫中心醫院(臺大癌醫) |
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