针对未经治疗的携带表皮生长因子受体突变的非鳞状 NSCLC 患者的奥希替尼联合贝伐单抗与奥希替尼单药随机 2 期研究的最终分析数据和探索性生物标志物分析：WJOG9717L研究

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2024-08-23 DOI:10.1016/j.jtocrr.2024.100716

Hirotsugu Kenmotsu MD, PhD , Kazuko Sakai PhD , Keita Mori PhD , Terufumi Kato MD , Shunichi Sugawara MD, PhD , Keisuke Kirita MD, PhD , Yasuto Yoneshima MD, PhD , Koichi Azuma MD, PhD , Kazumi Nishino MD, PhD , Shunsuke Teraoka MD , Ryo Koyama MD, PhD , Ken Masuda MD, PhD , Hidetoshi Hayashi MD, PhD , Ryo Toyozawa MD, PhD , Satoru Miura MD, PhD , Yuki Sato MD, PhD , Kazuhiko Nakagawa MD, PhD , Nobuyuki Yamamoto MD, PhD , Kazuto Nishio MD, PhD , Toshiaki Takahashi MD, PhD

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引用次数: 0

摘要

导言表皮生长因子受体（EGFR）酪氨酸激酶抑制剂一直是治疗表皮生长因子受体（EGFR）敏感突变的NSCLC患者的标准疗法。本研究揭示了奥希替尼联合贝伐单抗或奥希替尼单药治疗既往未经治疗的晚期表皮生长因子受体阳性非鳞癌 NSCLC 患者的生存数据、生物标志物和耐药机制的最终分析结果。在这项使用组织和血浆样本的探索性分析中，我们使用靶向深度测序技术评估了基线、疾病进展或最后一次用药时的基因图谱。结果经盲审的独立中央审查员审查，奥希替尼联合贝伐单抗治疗组的中位无进展生存期（PFS）为22.1个月，奥希替尼治疗组为20.2个月（危险比[HR] = 0.864，95%置信区间[CI]：0.549-1.359）。两组患者的3年总生存期没有差异（奥希莫替尼加贝伐单抗组：57.1%；奥希莫替尼加贝伐单抗组：57.1%）：HR 1.271，95% CI：0.727-2.223）。共有94名患者在基线时获得了可评估的血浆样本，40名患者获得了可评估的治疗前组织样本。基线血浆样本中检测到了表皮生长因子受体突变（76.6%）和TP53突变（44.7%）。在血浆TP53突变的患者（n = 42）中，经盲审的独立中央审查员评估，奥希替尼加贝伐单抗组的中位PFS为19.8个月，奥希替尼组的中位PFS为20.2个月（HR = 1.107，95% CI：0.534-2.297）。

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Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study

Introduction

EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive EGFR mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced EGFR-positive nonsquamous NSCLC.

Methods

We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing.

Results

The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727–2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. EGFR mutations (76.6%) and TP53 mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma TP53 mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534–2.297).