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病例报告:奥希替尼进展后,一名携带EGFR L858R-T790M-cis-G796S和L718Q耐药突变的非小细胞肺癌患者对布加替尼、西妥昔单抗联合埃克替尼的联合治疗产生持久反应。

Case Report: Durable Response to the Combination of Brigatinib and Cetuximab Plus Icotinib in a NSCLC Patient Harboring EGFR L858R-T790M-cis-G796S and L718Q Resistance Mutations Following Progression With Osimertinib.

作者信息

Wang Yubo, Han Rui, Zhu Mengxiao, He Tingting, He Yong

机构信息

Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, China.

出版信息

Front Oncol. 2022 Apr 21;12:875313. doi: 10.3389/fonc.2022.875313. eCollection 2022.

DOI:10.3389/fonc.2022.875313
PMID:35530305
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9071300/
Abstract

The efficacy of osimertinib is severely limited by the emergence of EGFR C797S, which is detected in either the cis or trans position with T790M when osimertinib is used as a second-line treatment, and which is largely identified in combination with an EGFR 19 deletion. The EGFR T790M-cis-G796S mutation, which also occurs in exon 20 as C797S, participates in osimertinib resistance. To date, limited data for overcoming this resistance mutation have been reported. Here, we report data for an advanced NSCLC patient who developed EGFR L858R-T790M-cis-G796S and EGFR L718Q resistance co-mutations following progression with osimertinib. Such a case has rarely been reported, and under chemotherapy guidelines for this situation, no other effective treatment is recommended. The patient in our case experienced remarkable clinical improvement and good tolerance to the combination target therapy of brigatinib and cetuximab plus icotinib. At the time of our patient's last follow-up and prior to publication, our patient had reached more than 9 months of progression-free survival (PFS) and felt very well. Our finding provides clinical evidence that the combined target therapy of brigatinib and cetuximab may potentially be an effective treatment strategy for patients with an acquired EGFR T790M-cis-G796S resistance mutation following osimertinib treatment.

摘要

奥希替尼的疗效因EGFR C797S的出现而受到严重限制,当奥希替尼用作二线治疗时,C797S在与T790M的顺式或反式位置被检测到,并且在很大程度上与EGFR 19外显子缺失同时存在。EGFR T790M-顺式-G796S突变也在第20外显子中作为C797S出现,参与奥希替尼耐药。迄今为止,关于克服这种耐药突变的有限数据已被报道。在此,我们报告了一名晚期非小细胞肺癌患者的数据,该患者在奥希替尼治疗进展后出现了EGFR L858R-T790M-顺式-G796S和EGFR L718Q耐药共突变。这种情况很少被报道,并且在针对这种情况的化疗指南下,不推荐其他有效治疗。我们病例中的患者在接受布加替尼、西妥昔单抗加埃克替尼的联合靶向治疗后,临床症状显著改善且耐受性良好。在我们患者的最后一次随访时以及在发表之前,我们的患者已达到超过9个月的无进展生存期(PFS),并且感觉良好。我们的发现提供了临床证据,表明布加替尼和西妥昔单抗的联合靶向治疗可能是奥希替尼治疗后获得性EGFR T790M-顺式-G796S耐药突变患者的一种有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/9071300/ea425c8a39f1/fonc-12-875313-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/9071300/ea425c8a39f1/fonc-12-875313-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f9/9071300/ea425c8a39f1/fonc-12-875313-g001.jpg

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