Kenmotsu Hirotsugu, Sakai Kazuko, Mori Keita, Kato Terufumi, Sugawara Shunichi, Kirita Keisuke, Yoneshima Yasuto, Azuma Koichi, Nishino Kazumi, Teraoka Shunsuke, Koyama Ryo, Masuda Ken, Hayashi Hidetoshi, Toyozawa Ryo, Miura Satoru, Sato Yuki, Nakagawa Kazuhiko, Yamamoto Nobuyuki, Nishio Kazuto, Takahashi Toshiaki
Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Japan.
Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
JTO Clin Res Rep. 2024 Aug 23;5(11):100716. doi: 10.1016/j.jtocrr.2024.100716. eCollection 2024 Nov.
EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive 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 -positive nonsquamous NSCLC.
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.
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. mutations (76.6%) and mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma 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).
There was also no significant difference in the PFS between the two arms, even in patients with mutations.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂一直是具有敏感突变的非小细胞肺癌（NSCLC）患者的标准治疗方法。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治疗的晚期EGFR阳性非鳞状NSCLC患者的最终分析生存数据、生物标志物和耐药机制。
我们之前报告了一项随机、开放标签的2期研究的主要结果，该研究比较了奥希替尼联合贝伐单抗与奥希替尼单药治疗该人群的疗效。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评估了基线、疾病进展或最后一剂时的基因谱。
由盲态独立中央审查员评估的无进展生存期（PFS）中位数，奥希替尼联合贝伐单抗组为22.1个月，奥希替尼组为20.2个月（风险比[HR]=0.864，95%置信区间[CI]：0.549-1.359）。两组的3年总生存率无差异（奥希替尼联合贝伐单抗：57.1%；奥希替尼单药治疗：65.0%；HR 1.271，95%CI：0.727-2.223）。共有94例患者在基线时有可评估的血浆样本，40例有可评估的治疗前组织样本。基线时血浆样本中检测到EGFR突变（76.6%）和TP53突变（44.7%）。在血浆EGFR突变患者（n=42）中，由盲态独立中央审查员评估的PFS中位数，奥希替尼联合贝伐单抗组为19.8个月，奥希替尼组为20.2个月（HR=1.107，95%CI：0.534-2.297）。
即使在EGFR突变患者中，两组的PFS也无显著差异。
