https://scholars.lib.ntu.edu.tw/handle/123456789/470770
標題: | Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: a genomic study | 作者: | CHIA-CHI LIN JIN-YUAN SHIH CHONG-JEN YU CHAO-CHI HO WEI-YU LIAO JIH-HSIANG LEE TZU-HSIU TSAI KANG-YI SU MIN-SHU HSIEH YIH-LEONG CHANG Bai Y.-Y. DE-RUI HUANG Thress K.S. CHIH-HSIN YANG |
公開日期: | 2018 | 出版社: | Lancet Publishing Group | 卷: | 6 | 期: | 2 | 起(迄)頁: | 107-116 | 來源出版物: | The Lancet Respiratory Medicine | 摘要: | Background: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. Methods: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma. Patients took 20–240 mg osimertinib per day until disease progression or development of intolerable side-effects. Plasma samples were collected every 6 weeks and tumour tissue biopsy was done at study entry and was optional after disease progression. We tested samples for resistance mechanisms, including EGFR-activating, Thr790Met, and Cys797Ser mutations, and assessed associations with overall survival, progression-free survival, and survival after disease progression. Findings: Of 71 patients enrolled in AURA, 53 were eligible for this analysis. Median progression-free survival was 11·1 months (95% CI 8·4–13·9) and overall survival was 16·9 months (11·7–29·1). 47 patients had disease progression. Median overall survival after osimertinib progression was 5·4 months (95% CI 4·1–10·0). Plasma samples were available for 40 patients after disease progression. 12 (30%) of these had the Thr790Met mutation (four of whom also had Cys797Ser mutations). Patients without detectable EGFR-activating mutations in plasma before treatment had the best overall and post-progression survival (22·4 months, 95% CI 15·6–not reached, and 10·8 months, 7·2–not reached, respectively). Loss of the Thr790Met mutation but presence of EGFR-activating mutations in plasma were associated with the shortest progression-free survival (median 2·6 months, 95% CI 1·3–not reached). In 22 post-progression tumour samples, we found one squamous cell and two small-cell transformations. We detected Thr790Met in nine (50%) of 18 samples, Cys797Ser in two (17%) of 12, cMET amplification in five (50%) of ten, BRAF mutation in one (8%) of 13, and KRAS mutation in one (8%) of 13. Interpretation: Heterogeneous resistance mechanisms developed in patients receiving osimertinib. Differences in resistance mechanisms might dictate future development strategies for osimertinib in clinical trials. Funding: AstraZeneca, Taiwan Ministry of Science and Technology. ? 2018 Elsevier Ltd |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85039450519&doi=10.1016%2fS2213-2600%2817%2930480-0&partnerID=40&md5=87eca8081190c7c2694555f9fba58d9e https://scholars.lib.ntu.edu.tw/handle/123456789/470770 |
ISSN: | 2213-2600 | DOI: | 10.1016/S2213-2600(17)30480-0 | SDG/關鍵字: | B Raf kinase; cysteine; epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; osimertinib; scatter factor receptor; serine; threonine; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; osimertinib; piperazine derivative; adult; aged; Article; blood sampling; BRAF gene; cancer resistance; cancer tissue; cell transformation; disease association; disease course; disease exacerbation; drug dose escalation; drug fatality; drug withdrawal; EGFR gene; female; gene activation; gene mutation; genomics; heart failure; human; human cell; human tissue; infection; major clinical study; male; non small cell lung cancer; oncogene; oncogene K ras; overall survival; pathophysiology; priority journal; progression free survival; skin disease; squamous cell; treatment failure; treatment outcome; tumor biopsy; tumor gene; antagonists and inhibitors; genetics; lung tumor; middle aged; mutation; non small cell lung cancer; retrospective study; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Genomics; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Piperazines; Receptor, Epidermal Growth Factor; Retrospective Studies |
顯示於: | 病理學科所 |
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