Asad Zadeh Vosta Kolaei Fatemeh, Cai Beilei, Kanakamedala Hemanth, Kim Julia, Doban Vitalii, Zhang Shiyu, Shi Michael
Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.
Genesis Research, Hoboken, NJ, United States.
Front Oncol. 2022 Feb 25;12:786124. doi: 10.3389/fonc.2022.786124. eCollection 2022.
exon 14 skipping mutation (ex14) is observed in ~3% of non-small cell lung cancer (NSCLC) cases and has been shown to be an independent poor prognostic factor associated with shorter overall disease-specific survival. Broad molecular testing can identify this biomarker in patients with advanced NSCLC (aNSCLC) and allow patients to be matched with the appropriate targeted therapy. This study examines biomarker testing patterns and clinical outcomes of chemotherapy and immuno-oncology (IO) monotherapy in aNSCLC patients with ex14.
A descriptive retrospective study was conducted using the Flatiron Health-Foundation Medicine Inc. (FMI) clinico-genomic database. Patients with ex14 aNSCLC treated with systemic therapies were included in the biomarker testing analysis. The duration from specimen collection to reported results was assessed for PD-L1- and ex14-tested patients. Clinical outcomes were assessed in patients treated with chemotherapy or IO monotherapy. First-line (1L) and second-line (2L) real-world progression-free survival (rw-PFS) were estimated using Kaplan-Meier analysis.
Of 91 ex14 patients eligible for the biomarker testing analysis, 77% and 60% received PD-L1 and FMI next-generation sequencing (NGS) testing within 3 months post aNSCLC diagnosis. Of those assessed for both PD-L1 and ex14 (n=9), the median duration between specimen collection and reporting was 1 week shorter for PD-L1 than for FMI NGS. Median 1L rw-PFS was 5.7 months (95% CI, 4.6-7.1) and 2.4 months (95% CI, 1.4-3.2) in patients receiving 1L chemotherapy (n=59) and IO monotherapy (n=18), with 3-month 1L rw-PFS rates of 78% and 33%. Median 2L rw-PFS was 3.5 months (95% CI, 1.9-11.1) and 4.7 months (95% CI, 2.8-12.9) in patients receiving 2L chemotherapy (n=16) and IO monotherapy (n=23), with 3-month 2L rw-PFS rates of 54% and 67%.
The median time from biopsy to test results appears 1 week shorter for PD-L1 than for FMI NGS. Chemotherapy and IO monotherapy were the most common regimens utilized but with limited PFS.
外显子14跳跃突变（ex14）在约3%的非小细胞肺癌（NSCLC）病例中被观察到，并且已被证明是一个与总体疾病特异性生存期较短相关的独立不良预后因素。广泛的分子检测可以在晚期NSCLC（aNSCLC）患者中识别出这种生物标志物，并使患者能够接受合适的靶向治疗。本研究探讨了aNSCLC伴ex14患者的生物标志物检测模式以及化疗和免疫肿瘤学（IO）单药治疗的临床结局。
使用Flatiron Health- Foundation Medicine公司（FMI）的临床基因组数据库进行了一项描述性回顾性研究。接受全身治疗的ex14 aNSCLC患者被纳入生物标志物检测分析。对接受PD-L1检测和ex14检测的患者评估了从标本采集到报告结果的时间。对接受化疗或IO单药治疗的患者评估了临床结局。使用Kaplan-Meier分析估计一线（1L）和二线（2L）真实世界无进展生存期（rw-PFS）。
在91例符合生物标志物检测分析条件的ex14患者中，77%和60%在aNSCLC诊断后3个月内接受了PD-L1检测和FMI下一代测序（NGS）检测。在同时接受PD-L1和ex14评估的患者中（n = 9），PD-L1检测从标本采集到报告的中位时间比FMI NGS短1周。接受1L化疗（n = 59）和IO单药治疗（n = 18）的患者，1L rw-PFS的中位数分别为5.7个月（95%CI，4.6 - 7.1）和2.4个月（95%CI，1.4 - 3.2），3个月时的1L rw-PFS率分别为78%和33%。接受2L化疗（n = 16）和IO单药治疗（n = 23）的患者，2L rw-PFS的中位数分别为3.5个月（95%CI，1.9 - 11.1）和4.7个月（95%CI，2.8 - 12.9），3个月时的2L rw-PFS率分别为54%和67%。
PD-L1检测从活检到检测结果的中位时间似乎比FMI NGS短1周。化疗和IO单药治疗是最常用的方案，但无进展生存期有限。
