文章：

一项关于奥希替尼治疗晚期非小细胞肺癌患者的II期研究：患者既往接受过表皮生长因子受体酪氨酸激酶抑制剂治疗，并通过血浆循环肿瘤DNA检测到EGFR和T790M突变（PLASMA研究）

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)

原文发布日期：16 October 2023

DOI: 10.3390/cancers15204999

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

表皮生长因子受体（EGFR）T790M突变导致约50%的晚期非小细胞肺癌（NSCLC）患者在接受第一/二代（1G/2G）EGFR酪氨酸激酶抑制剂（TKIs）治疗后出现疾病进展，并对奥希替尼敏感。组织取样是T790M检测的金标准方法，但具有侵入性。本研究评估了奥希替尼在循环肿瘤DNA（ctDNA）中检出EGFR突变及T790M突变的NSCLC患者中的疗效。PLASMA是一项前瞻性、开放标签、多中心单臂II期研究。入组患者为晚期NSCLC，在≥一种1G/2G TKI治疗后进展时血浆中检出敏感EGFR突变及T790M突变，每日接受80 mg奥希替尼治疗直至疾病进展。主要终点为客观缓解率（ORR）；次要终点包括无进展生存期（PFS）、总生存期（OS）、疾病控制率（DCR）及毒性反应。采用血浆新一代测序技术确定奥希替尼耐药机制并评估系列ctDNA变化。2017年至2019年间，共纳入来自5个国家8个中心的110例患者。中位随访时间为2.64（IQR 2.44–3.12）年。ORR为50.9%（95% CI 41.2–60.6），DCR为84.5%（95% CI 76.4–90.7）。中位PFS为7.4（95% CI 6.0–9.3）个月；中位OS为1.63（95% CI 1.35–2.16）年。所有患者中，76%出现治疗相关不良事件（TRAEs），最常见为甲沟炎（22.7%）；11%发生≥3级TRAEs。ctDNA基线负荷及其动态变化具有预后价值。奥希替尼对1G/2G TKIs治疗后ctDNA检测检出敏感EGFR突变及T790M突变的NSCLC患者具有明确疗效。

原文链接：

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)