Lau Sally C M, Perdrizet Kirstin, Fung Andrea S, Mata Danilo Giffoni M M, Weiss Jessica, Holzapfel Nick, Liu Geoffrey, Bradbury Penelope A, Shepherd Frances A, Sacher Adrian G, Feilotter Harriet, Sheffield Brandon, Hwang David, Tsao Ming Sound, Cheng Susanna, Cheema Parneet, Leighl Natasha B
Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Department of Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University (NYU) Langone Health, NYU Grossman School of Medicine, New York, New York.
JTO Clin Res Rep. 2023 Aug 19;4(10):100562. doi: 10.1016/j.jtocrr.2023.100562. eCollection 2023 Oct.
NSCLC with exon 14 skipping mutation (ex14) is associated with poor outcomes. Integration of novel targeted therapies is challenging because of barriers in testing and drug access. We, therefore, sought to characterize the treatment patterns, outcomes, and emerging issues of treatment sequencing in patients with ex14-mutant NSCLC.
We reviewed all NSCLC cases with ex14 alterations between 2014 and 2020 across four Canadian cancer centers. Demographics, disease characteristics, systemic therapy, overall response rates (ORRs), survival, and toxicity were summarized.
Among 64 patients with ex14-mutant NSCLC, the median overall survival was 23.1 months: 127.0 months in stage 1, 27.3 months in resected stage 2 and 3, and 16.6 months in unresectable stage 3 or 4 disease, respectively. In patients with advanced disease, 22% were too unwell for systemic treatment. MET tyrosine kinase inhibitors (TKIs) were administered to 28 patients with an ORR of 33%, median progression-free survival of 2.7 months, and 3.8 months for selective TKIs. Programmed cell death protein-1 (PD-1) inhibitors were given to 25 patients-the ORR was 44% and progression-free survival was 10.6 months. No responses were seen with subsequent MET TKIs after initial TKI treatment. Grade 3 or higher toxicities occurred in 64% of patients who received MET TKI after PD-1 inhibitors versus 8% in those who did not receive PD-1 inhibitors.
Many patients with advanced ex14 NSCLC were too unwell to receive treatment. PD-1 inhibitors seem effective as an initial treatment, although greater toxicity was seen with subsequent MET TKIs. Thus, timely testing for ex14 skipping and initial therapy are imperative to improving patient survival.
具有外显子14跳跃突变（ex14）的非小细胞肺癌（NSCLC）与不良预后相关。由于检测和药物获取方面的障碍，新型靶向治疗的整合具有挑战性。因此，我们试图描述ex14突变型NSCLC患者的治疗模式、结局以及治疗顺序中出现的问题。
我们回顾了2014年至2020年期间加拿大四个癌症中心所有具有ex14改变的NSCLC病例。总结了人口统计学、疾病特征、全身治疗、总缓解率（ORR）、生存率和毒性。
在64例ex14突变型NSCLC患者中，中位总生存期为23.1个月：1期为127.0个月，2期和3期切除术后为27.3个月，不可切除的3期或4期疾病为16.6个月。在晚期疾病患者中，22%的患者身体状况太差无法接受全身治疗。28例患者接受了MET酪氨酸激酶抑制剂（TKI）治疗，ORR为33%，中位无进展生存期为2.7个月，选择性TKI为3.8个月。25例患者接受了程序性细胞死亡蛋白1（PD-1）抑制剂治疗，ORR为44%，无进展生存期为10.6个月。初始TKI治疗后，后续MET TKI未观察到缓解。在接受PD-1抑制剂后接受MET TKI的患者中，64%发生3级或更高毒性，而未接受PD-1抑制剂的患者中这一比例为8%。
许多晚期ex14 NSCLC患者身体状况太差无法接受治疗。PD-1抑制剂似乎作为初始治疗有效，尽管后续MET TKI的毒性更大。因此，及时检测ex14跳跃和初始治疗对于提高患者生存率至关重要。
