Impact of PD-L1 Expression on the Overall Survival of Caucasian Patients with Advanced EGFR-Mutant NSCLC Treated with Frontline Osimertinib.

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2024-07-01 Epub Date: 2024-06-03 DOI:10.1007/s11523-024-01072-x

Thomas Papazyan, Marc G Denis, Christine Sagan, Judith Raimbourg, Guillaume Herbreteau, Elvire Pons-Tostivint

{"title":"Impact of PD-L1 Expression on the Overall Survival of Caucasian Patients with Advanced EGFR-Mutant NSCLC Treated with Frontline Osimertinib.","authors":"Thomas Papazyan, Marc G Denis, Christine Sagan, Judith Raimbourg, Guillaume Herbreteau, Elvire Pons-Tostivint","doi":"10.1007/s11523-024-01072-x","DOIUrl":null,"url":null,"abstract":"Background: The treatment of advanced non-small cell lung cancer (NSCLC) harboring an oncogenic epidermal growth factor receptor mutation (EGFRm) is currently based on osimertinib, a third-generation tyrosine kinase inhibitor (TKI). High Programmed death ligand 1 (PD-L1) expression ≥ 50% demonstrated to be a negative prognostic factor, mostly among Asian populations treated with 1st/2nd generation TKI.Objective: We investigated the impact of PD-L1 expression on the progression free survival (PFS) and overall survival (OS) within a cohort of patients receiving osimertinib as first-line treatment.Methods: Our bi-centre French retrospective study included all newly diagnosed patients with an advanced EGFRm (common and uncommon) NSCLC, between May 2018 and November 2022, treated with osimertinib. The primary endpoint was OS according to tumor proportion score PD-L1 expression (low/intermediate < 50% vs high ≥ 50%). Survival analyses were performed using Kaplan-Meier method and Cox model for adjusted multivariate analysis.Results: Of 96 patients, median age was 71 (IQR 62-76), 70 were women (72.9%), 81 had a performance status (PS) 0-1 (84.3%). Median follow-up was 22.6 months (95% CI 20.5-24.7). Twenty patients (20.8%) had high PD-L1 expression ≥ 50%. No significant differences in baseline characteristics were observed based on PD-L1 status. Patients with PD-L1 ≥ 50% had significant shorter PFS and OS than those with PD-L1 < 50%, respectively 9.3 vs 17.5 months (p = 0.044 months) and 14.3 vs 26.0 months (p = 0.025). Multivariable adjustment for baseline characteristics found that PS ≥ 2 (HR 2.79, 95% CI 1.12-6.93, p = 0.027), PD-L1 ≥ 50% (HR 2.61, 95% CI 1.31 to 5.22, p = 0.007) and uncommon EGFR mutation (HR 4.59, 95% CI 1.95-10.80, p = <0.001) were associated with a shorter OS. Brain metastases at diagnosis and age ≥ 65 were not, respectively HR 1.66 (95% CI 0.90-3.06, p = 0.11) and HR 0.95 (95% CI 0.50-1.80, p=0.9).Conclusions: Our study found that PD-L1 expression ≥ 50% was associated with a shorter OS in EGFRm NSCLC patients treated with first line osimertinib. Further research is warranted to understand the underlying molecular and cellular mechanisms of this correlation.","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"611-621"},"PeriodicalIF":4.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Targeted Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11523-024-01072-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: The treatment of advanced non-small cell lung cancer (NSCLC) harboring an oncogenic epidermal growth factor receptor mutation (EGFRm) is currently based on osimertinib, a third-generation tyrosine kinase inhibitor (TKI). High Programmed death ligand 1 (PD-L1) expression ≥ 50% demonstrated to be a negative prognostic factor, mostly among Asian populations treated with 1st/2nd generation TKI.

Objective: We investigated the impact of PD-L1 expression on the progression free survival (PFS) and overall survival (OS) within a cohort of patients receiving osimertinib as first-line treatment.

Methods: Our bi-centre French retrospective study included all newly diagnosed patients with an advanced EGFRm (common and uncommon) NSCLC, between May 2018 and November 2022, treated with osimertinib. The primary endpoint was OS according to tumor proportion score PD-L1 expression (low/intermediate < 50% vs high ≥ 50%). Survival analyses were performed using Kaplan-Meier method and Cox model for adjusted multivariate analysis.

Results: Of 96 patients, median age was 71 (IQR 62-76), 70 were women (72.9%), 81 had a performance status (PS) 0-1 (84.3%). Median follow-up was 22.6 months (95% CI 20.5-24.7). Twenty patients (20.8%) had high PD-L1 expression ≥ 50%. No significant differences in baseline characteristics were observed based on PD-L1 status. Patients with PD-L1 ≥ 50% had significant shorter PFS and OS than those with PD-L1 < 50%, respectively 9.3 vs 17.5 months (p = 0.044 months) and 14.3 vs 26.0 months (p = 0.025). Multivariable adjustment for baseline characteristics found that PS ≥ 2 (HR 2.79, 95% CI 1.12-6.93, p = 0.027), PD-L1 ≥ 50% (HR 2.61, 95% CI 1.31 to 5.22, p = 0.007) and uncommon EGFR mutation (HR 4.59, 95% CI 1.95-10.80, p = <0.001) were associated with a shorter OS. Brain metastases at diagnosis and age ≥ 65 were not, respectively HR 1.66 (95% CI 0.90-3.06, p = 0.11) and HR 0.95 (95% CI 0.50-1.80, p=0.9).

Conclusions: Our study found that PD-L1 expression ≥ 50% was associated with a shorter OS in EGFRm NSCLC patients treated with first line osimertinib. Further research is warranted to understand the underlying molecular and cellular mechanisms of this correlation.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

PD-L1表达对接受奥希替尼前线治疗的高加索晚期表皮生长因子受体突变NSCLC患者总生存期的影响

背景：对于携带致癌表皮生长因子受体突变（EGFRm）的晚期非小细胞肺癌（NSCLC），目前主要采用第三代酪氨酸激酶抑制剂（TKI）奥西美替尼（osimertinib）进行治疗。程序性死亡配体1（PD-L1）高表达≥50%被证明是一个负面预后因素，主要发生在接受第一代/第二代TKI治疗的亚洲人群中：我们研究了在接受奥希替尼一线治疗的患者队列中，PD-L1表达对无进展生存期（PFS）和总生存期（OS）的影响：我们的法国双中心回顾性研究纳入了2018年5月至2022年11月期间所有新确诊的晚期表皮生长因子受体m（常见和不常见）NSCLC患者，他们均接受了奥希替尼治疗。主要终点是根据肿瘤比例评分PD-L1表达（低/中<50% vs 高≥50%）得出的OS。采用Kaplan-Meier方法进行生存期分析，并使用Cox模型进行调整后的多变量分析：在96名患者中，中位年龄为71岁（IQR 62-76），70名为女性（72.9%），81名患者的表现状态（PS）为0-1（84.3%）。中位随访时间为 22.6 个月（95% CI 20.5-24.7）。20名患者（20.8%）的PD-L1高表达率≥50%。根据PD-L1状态，基线特征无明显差异。PD-L1≥50%的患者的PFS和OS明显短于PD-L1＜50%的患者，分别为9.3个月 vs 17.5个月（p = 0.044个月）和14.3个月 vs 26.0个月（p = 0.025）。对基线特征进行多变量调整后发现，PS≥2（HR 2.79，95% CI 1.12-6.93，p = 0.027）、PD-L1≥50%（HR 2.61，95% CI 1.31-5.22，p = 0.007）和不常见的表皮生长因子受体突变（HR 4.59，95% CI 1.95-10.80，p = 结论：PS≥2、PD-L1≥50%和不常见的表皮生长因子受体突变（HR 4.59）均可导致患者的生存期缩短：我们的研究发现，PD-L1表达≥50%与一线奥希替尼治疗的EGFRm NSCLC患者较短的OS相关。要了解这种相关性的潜在分子和细胞机制，还需要进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.