Evidera, Montreal, QC, Canada.
Evidera, London, United Kingdom.
PLoS One. 2021 Mar 8;16(3):e0247620. doi: 10.1371/journal.pone.0247620. eCollection 2021.
The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins.
Searches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year.
Seventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with other EGFR mutations and EGFR wildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common.
Findings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.
表皮生长因子受体（EGFR）外显子 20 插入突变（Exon 20ins）在非小细胞肺癌中的负担尚不清楚。进行了系统评价，以确定与 Exon 20ins 相关的突变频率、预后影响、临床、患者报告和经济结局的证据。
在 Embase 和 Medline 中进行了检索，并补充了最近的会议记录。纳入的研究不受干预、地理位置或出版年份的限制。
共纳入 78 项独特的研究；53 项报告了突变频率，13 项报告了预后影响，36 项报告了临床结局，1 项报告了人文负担。未确定经济负担数据。Exon 20ins 突变的频率范围为所有 NSCLC 病例的 0.1%至 4%，以及所有 EGFR 突变的 1%至 12%。Exon 20ins 突变的预后影响数据存在异质性，但强调了与其他 EGFR 突变和 EGFR 野生型相比，接受 Exon 20ins 突变治疗的患者结局更差，涉及广泛的治疗和治疗线。关于现有治疗方法的临床疗效和安全性的比较证据有限，报告真实世界疗效的研究样本量也有限。9 项单臂试验和 27 项观察性研究报告了 Exon 20ins 患者的临床结局。与 TKI 相比，化疗作为一线治疗时，观察到生存和缓解趋势更好。对于后续治疗线，新型靶向治疗提供了令人鼓舞的初步反应，而化疗的结果则不太理想。报告的安全性数据有限。一篇会议摘要描述了 Exon 20ins 患者的症状负担，疲劳和疼痛最为常见。
系统评价的结果表明，exon 20ins 患者对安全有效的治疗方法存在高度未满足的需求，需要进一步开展证据生成工作，以更好地了解这些患者的患者层面和经济影响。
