Exploring the impact of patient-specific clinical features on osimertinib effectiveness in a real-world cohort of patients with EGFR mutated non-small cell lung cancer

IF 5.7 2区 医学 Q1 ONCOLOGY
Ard van Veelen, G. D. Marijn Veerman, Marjon V. Verschueren, Judith L. Gulikers, Christi M. J. Steendam, Anita J. W. M. Brouns, Safiye Dursun, Marthe S. Paats, Vivianne C. G. Tjan-Heijnen, Cor van der Leest, Anne-Marie C. Dingemans, Ron H. J. Mathijssen, Ewoudt M. W. van de Garde, Patrick Souverein, Johanna H. M. Driessen, Lizza E. L. Hendriks, Robin M. J. M. van Geel, Sander Croes
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引用次数: 1

Abstract

Osimertinib is prescribed to patients with metastatic non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation. Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter cohort study. Eligible patients were ≥18 years, with metastatic EGFRm+ NSCLC, receiving osimertinib. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analyses and multivariate Cox proportional hazard models were performed. In total, 294 patients were included. Primary EGFR-mutations were mainly exon 19 deletions (54%) and p.L858R point mutations (30%). Osimertinib was given in first-line (40%), second-line (46%) or beyond (14%), with median PFS 14.4 (95% CI: 9.4-19.3), 13.9 (95% CI: 11.3-16.1) and 8.7 months (95% CI: 4.6-12.7), respectively. Patients with low BMI (<20.0 kg/m2) had significantly shorter PFS/OS compared to all other subgroups. Patients with a high plasma trough concentration in steady state (Cmin,SS; >271 ng/mL) had shorter PFS compared to a low Cmin,SS (<163 ng/mL; aHR 2.29; 95% CI: 1.13-4.63). A significant longer PFS was seen in females (aHR = 0.61, 95% CI: 0.45-0.82) and patients with the exon 19 deletion (aHR = 0.58, 95% CI: 0.36-0.92). A trend towards longer PFS was seen for TP53 wild-type patients, while age did not impact PFS. Patients with a primary EGFR exon 19 deletion had longer PFS, while a low BMI, male sex and a high Cmin,SS were indicative for shorter PFS and/or OS. Age was not associated with effectiveness outcomes of osimertinib.

Abstract Image

在EGFR突变非小细胞肺癌癌症患者的现实世界队列中,探讨患者特异性临床特征对奥西替尼有效性的影响。
奥西美替尼适用于转移性癌症(NSCLC)和致敏EGFR突变的患者。关于患者特征或奥西替尼暴露对疗效结果的影响,现有数据有限。这是一项荷兰多中心队列研究。符合条件的患者≥18 年,转移性EGFRm+NSCLC,接受奥西替尼治疗。主要终点是无进展生存期(PFS)。次要终点包括总生存期(OS)和安全性。进行Kaplan-Meier分析和多变量Cox比例风险模型。总共包括294名患者。原发性EGFR突变主要为外显子19缺失(54%)和p.L858R点突变(30%)。奥西美替尼用于一线(40%)、二线(46%)或以上(14%),中位PFS 14.4(95%CI:9.4-19.3)、13.9(95%CI:11.3-16.1)和8.7 月(95%CI:4.6-12.7)。与所有其他亚组相比,低BMI(2)患者的PFS/OS明显更短。稳定状态下血浆谷浓度高的患者(Cmin,SS;>271 ng/mL)与低Cmin、SS(min、SS表示PFS和/或OS较短。年龄与奥西替尼的有效性结果无关。
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来源期刊
CiteScore
13.40
自引率
3.10%
发文量
460
审稿时长
2 months
期刊介绍: The International Journal of Cancer (IJC) is the official journal of the Union for International Cancer Control—UICC; it appears twice a month. IJC invites submission of manuscripts under a broad scope of topics relevant to experimental and clinical cancer research and publishes original Research Articles and Short Reports under the following categories: -Cancer Epidemiology- Cancer Genetics and Epigenetics- Infectious Causes of Cancer- Innovative Tools and Methods- Molecular Cancer Biology- Tumor Immunology and Microenvironment- Tumor Markers and Signatures- Cancer Therapy and Prevention
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