Molecular characterization and clinical outcomes in EGFR-mutant de novo MET-overexpressed advanced non-small-cell lung cancer.
Molecular characterization and clinical outcomes in EGFR-mutant de novo MET-overexpressed advanced non-small-cell lung cancer.
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DOI：
10.1016/j.esmoop.2021.100347
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发表时间：
2022-03
期刊：
影响因子：
7.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Mi J;Huang Z;Zhang R;Zeng L;Xu Q;Yang H;Lizaso A;Tong F;Dong X;Yang N;Zhang Y
约2%-8%的非小细胞肺癌（NSCLC）在EGFR-酪氨酸激酶抑制剂（EGFR-TKI）治疗前同时存在表皮生长因子受体（EGFR）致敏突变和间充质-上皮转化因子（MET）扩增。本研究旨在探讨EGFR突变、MET过表达/扩增的晚期NSCLC患者的最佳一线治疗选择。采用免疫组化确定了共计104例EGFR突变型新发MET过度表达的晚期NSCLC初治患者，并根据治疗方案分为4组：EGFR-TKI单药治疗（n = 48）、EGFR-TKI联合克唑替尼（n = 9）或化疗（n = 12）以及化疗（n = 35）。还用下一代测序（NGS）测试了28名患者的亚群。根据治疗策略和分子特征分析客观缓解率（ORR）和无进展生存期（PFS）结局。所有患者（n = 104）的ORR为36.5%，中位PFS（mPFS）为7.0个月。四个治疗组的基线临床病理学特征相似。与化疗相比，EGFR-TKI单药治疗或EGFR-TKI联合治疗的ORR显著更高（P < 0.001），mPFS更长（P = 0.003）。在EGFR-TKI单药治疗和联合治疗之间未观察到ORR或PFS差异。在确定的NGS人群（n = 28）中，接受EGFR-TKI+克唑替尼治疗的患者（n = 9）获得了相似的ORR（88.9% vs 57.9%，P = 0.195）和mPFS（9.0 vs 8.5个月，风险比1.10，95%置信区间0.43-2.55，P = 0.45），而接受EGFR-TKI单药治疗（n = 19），无论MET拷贝数状态如何。接受EGFR-TKI+克唑替尼治疗的患者中3/4级皮疹显著更多（P = 0.026）。我们的研究结果提供了临床证据，表明同时存在EGFR致敏突变和新发MET扩增/过表达的患者可以从一线EGFR-TKI单药治疗中获益。在2.6%的肺癌患者中检测到伴随的EGFR致敏突变和MET过表达/扩增。与化疗相比，EGFR-TKI单药治疗的缓解率更高，PFS更长。无论MET拷贝数如何，EGFR-TKI联合或不联合克唑替尼均可产生相当的PFS。EGFR-TKI单药治疗的3/4级不良事件数量低于EGFR-TKI+克唑替尼。
Approximately 2%-8% of non-small-cell lung cancer (NSCLC) harbors concurrent epidermal growth factor receptor (EGFR) sensitizing mutation and mesenchymal–epithelial transition factor (MET) amplification prior to EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. This study aimed to investigate the optimal first-line therapeutic options for patients with concurrent EGFR-mutant, MET-overexpressed/amplified advanced NSCLC. A total of 104 treatment-naïve patients with EGFR-mutant de novo MET-overexpressed advanced NSCLC were identified using immunohistochemistry and stratified to four groups according to treatment regimen: EGFR-TKI monotherapy (n = 48), EGFR-TKI combined with either crizotinib (n = 9) or chemotherapy (n = 12), and chemotherapy (n = 35). A subpopulation of 28 patients was also tested with next-generation sequencing (NGS). Objective response rate (ORR) and progression-free survival (PFS) outcomes were analyzed according to treatment strategies and molecular features. All the patients (n = 104) achieved ORR of 36.5% and median PFS (mPFS) of 7.0 months. Baseline clinicopathologic characteristics were similar among the four treatment groups. Compared with chemotherapy, EGFR-TKI monotherapy or EGFR-TKI combination therapy achieved significantly higher ORR (P < 0.001) and longer mPFS (P = 0.003). No ORR or PFS difference was observed between EGFR-TKI monotherapy and combination therapy. In the NGS-identified population (n = 28), patients who received EGFR-TKI plus crizotinib (n = 9) achieved similar ORR (88.9% versus 57.9%, P = 0.195) and mPFS (9.0 versus 8.5 months, hazard ratio 1.10, 95% confidence interval 0.43-2.55, P = 0.45) than those who received EGFR-TKI monotherapy (n = 19), regardless of MET copy number status. Grade 3/4 rashes were significantly more among patients who received EGFR-TKI plus crizotinib (P = 0.026). Our findings provided clinical evidence that patients with concurrent EGFR sensitizing mutation and de novo MET amplification/overexpression could benefit from first-line EGFR-TKI monotherapy. Concomitant EGFR sensitizing mutation and MET overexpression/amplification were detected in 2.6% of lung cancer patients. EGFR-TKI monotherapy elicited a higher response rate and longer PFS than chemotherapy. EGFR-TKI with or without crizotinib elicited comparable PFS regardless of MET copy number. EGFR-TKI monotherapy achieved lower number of grade 3/4 adverse events than EGFR-TKI plus crizotinib.
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影响因子：
45.3
作者：
Lai, Gillianne Gy;Lim, Tse Hui;Tan, Daniel S. W.
通讯作者：
Tan, Daniel S. W.
影响因子：
51.1
作者：
Sequist, Lecia, V;Han, Ji-Youn;Oxnard, Geoffrey
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Oxnard, Geoffrey
影响因子：
20.4
作者：
Guo, Robin;Berry, Lynne D.;Kris, Mark G.
通讯作者：
Kris, Mark G.
影响因子：
3.4
作者：
Saigi, M.;McLeer-Florin, A.;Sanchez-Cespedes, M.
通讯作者：
Sanchez-Cespedes, M.
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William