奥希替尼治疗非小细胞肺癌及罕见肿瘤表皮生长因子受体突变患者的安全性和有效性：系统评价和单臂荟萃分析。

Safety and Efficacy of Osimertinib in Patients With Non-Small-Cell Lung Cancer and Uncommon Tumoral Epidermal Growth Factor Receptor Mutations: A Systematic Review and Single-Arm Meta-Analysis.

机构信息

Department of Internal Medicine, School of Medicine, Federal University of Amazonas-UFAM, Manaus, Brazil.

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.

出版信息

JCO Precis Oncol. 2024 Nov;8:e2400331. doi: 10.1200/PO.24.00331. Epub 2024 Nov 22.

DOI:10.1200/PO.24.00331

PMID:39576954

Abstract

PURPOSE

The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor () mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic mutations.

METHODS

PubMed, Embase, and the Cochrane Library were searched for eligible studies reporting the efficacy and safety of osimertinib in NSCLC with uncommon mutations defined as any mutations other than exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Then, we performed a meta-analysis to pool survival outcomes and antitumoral activity, including intracranial (ic) response and adverse events.

RESULTS

Fifteen studies comprising 594 patients were included. The most frequently observed uncommon solitary mutations were G719X in 25% (81/327) of patients and L861Q in 21% (69/327). The most common compound mutations were G719X with T790M in 12% (23/192) of patients and G719X with S768I in 11% (22/192). Pooled analysis showed an objective response rate (ORR) of 51.30% (95% CI, 45.80 to 56.81), a disease control rate (DCR) of 90.11% (95% CI, 86.27 to 92.96), a median progression-free survival of 9.71 months (95% CI, 7.96 to 11.86), and a median overall survival of 16.79 months (95% CI, 9.93 to 28.39). icORR was 45.96% (95% CI, 30.18 to 62.17), and icDCR was 95.76% (95% CI, 69.84 to 100). Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33).

CONCLUSION

Osimertinib demonstrated robust response in NSCLC harboring uncommon mutations, without unanticipated safety concerns.

摘要

目的

奥希替尼在非小细胞肺癌（NSCLC）中常见的表皮生长因子受体（EGFR）突变中活性尚未完全确定。因此，我们进行了系统评价和荟萃分析，以评估奥希替尼在 NSCLC 中罕见体细胞突变患者中的安全性和疗效。

方法

检索 PubMed、Embase 和 Cochrane 图书馆，以评估奥希替尼在 NSCLC 中罕见的 EGFR 突变患者中的安全性和疗效，罕见的 EGFR 突变定义为除外显子 19 缺失、L858R 和 T790M 突变以及外显子 20 插入之外的任何突变，除非存在复合突变。然后，我们进行荟萃分析以汇总生存结果和抗肿瘤活性，包括颅内（ic）反应和不良事件。

结果

共纳入 15 项研究，包括 594 例患者。最常见的罕见单突变是 G719X（占 25%，81/327）和 L861Q（占 21%，69/327）。最常见的复合突变是 G719X 与 T790M（占 12%，23/192）和 G719X 与 S768I（占 11%，22/192）。汇总分析显示客观缓解率（ORR）为 51.30%（95%CI，45.80 至 56.81），疾病控制率（DCR）为 90.11%（95%CI，86.27 至 92.96），中位无进展生存期为 9.71 个月（95%CI，7.96 至 11.86），中位总生存期为 16.79 个月（95%CI，9.93 至 28.39）。颅内缓解率（icORR）为 45.96%（95%CI，30.18 至 62.17），颅内疾病控制率（icDCR）为 95.76%（95%CI，69.84 至 100）。奥希替尼耐受性良好，3 级或以上不良事件发生率为 21.77%（95%CI，6.24 至 43.33）。