Ji Jingran, Aredo Jacqueline V, Piper-Vallillo Andrew, Huppert Laura, Rotow Julia K, Husain Hatim, Stewart Susan, Cobb Rosemary, Wakelee Heather A, Blakely Collin M, Wong Melisa L, Gubens Matthew A, Madani Mohammad H, Digumarthy Subba R, McCoach Caroline, Piotrowska Zofia, Neal Joel W, Riess Jonathan W
City of Hope Comprehensive Cancer Center, Duarte, California.
UC Davis Comprehensive Cancer Center, Sacramento, California.
JTO Clin Res Rep. 2023 Jan 10;4(3):100459. doi: 10.1016/j.jtocrr.2022.100459. eCollection 2023 Mar.
mutations drive a subset of NSCLC. Patients harboring the common mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical mutations.
Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed.
A total of 50 patients with NSCLC with uncommon mutations were identified. The most frequent mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5-12.9 mo) overall and 10.7 months (95% CI: 3.2-18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%-48.1%) overall and 41.2% (95% CI: 18.4%-67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations.
Osimertinib has activity in patients with NSCLC harboring atypical mutations. Osimertinib activity differs by the type of atypical -activating mutation.
突变驱动了一部分非小细胞肺癌（NSCLC）。携带常见突变（外显子19缺失和L858R）的患者对第三代酪氨酸激酶抑制剂奥希替尼反应良好。然而，奥希替尼对具有非典型突变的NSCLC的作用尚未得到充分描述。这项多中心回顾性研究评估了奥希替尼在患有非典型突变的NSCLC患者中的疗效。
纳入来自美国六个学术癌症中心的接受奥希替尼治疗的转移性NSCLC患者，这些患者至少携带一种非典型突变，排除同时存在的外显子19缺失、L858R或T790M突变。收集基线临床特征。主要终点是奥希替尼的治疗中断时间（TTD）。还根据实体瘤疗效评价标准第1.1版评估客观缓解率。
共确定了50例具有罕见突变的NSCLC患者。最常见的突变是L861Q（40%，n = 18）、G719X（28%，n = 14）和外显子20插入（14%，n = 7）。奥希替尼的中位TTD总体为9.7个月（95%置信区间[CI]：6.5 - 12.9个月），一线治疗时为10.7个月（95%CI：3.2 - 18.1个月）（n = 20）。总体客观缓解率为31.7%（95%CI：18.1% - 48.1%），一线治疗时为41.2%（95%CI：18.4% - 67.1%）。L861Q（17.2个月）、G719X（7.8个月）和外显子20插入（1.5个月）突变患者的中位TTD有所不同。
奥希替尼对携带非典型突变的NSCLC患者有活性。奥希替尼的活性因非典型激活突变的类型而异。
