Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation, T790M, and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy
Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation, T790M, and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy
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布加替尼和西妥昔单抗联合疗法有效治疗携带 EGFR 激活突变、T790M 和 cis-C797S 三重突变的肺腺癌
DOI：
10.1016/j.jtho.2020.04.014
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发表时间：
2020-08-01
影响因子：
20.4
通讯作者：
He, Yong
中科院分区：
文献类型：
--
作者：
Wang, Yubo;Yang, Nong;He, Yong
前言：EGFR cis-C797S介导的奥西美替尼获得性耐药是一个日益严峻的挑战。目前还没有有效的治疗策略来克服顺式C797S介导的耐药性。方法：在这项回顾性队列研究中，通过下一代靶向测序，确定了15例晚期肺腺癌并伴有EGFR激活突变的T790M和顺式C797S。结果：在5例EGFR 19del-T790M-cis-C797S突变阳性患者中，3例部分缓解，2例病情稳定，总的客观有效率为60%，疾病控制率为100%。在10例EGFR 19del或L858R-T790M-cis-C797S突变阳性并接受化疗的患者中，仅1例部分缓解，5例病情稳定，其余4例未受益于化疗，总体客观缓解率和疾病控制率分别为10%和60%。接受联合靶向治疗的患者的中位无进展生存期为14个月，接受化疗的患者的中位无进展生存期为3个月。结论：我们的回顾性研究提供了临床证据，表明联合靶向治疗对获得EGFR T790M-cis-C797S介导的奥西美替尼耐药的患者是有益的，并且可能是一种有效的治疗策略。(C)2020年国际肺癌研究协会。爱思唯尔公司出版，版权所有。
Introduction: Acquired resistance to osimertinib mediated by EGFR cis-C797S is now a growing challenge. No effective treatment strategy is currently available to overcome cis-C797S-mediated resistance.Methods: In this retrospective cohort study, 15 patients with advanced lung adenocarcinoma and EGFR-activating mutation, T790M, and cis-C797S after osimertinib progression were identified by targeted next-generation sequencing. Five of these patients received a combined therapy of brigatinib and cetuximab, and 10 patients received cisplatin-based doublet chemotherapy.Results: Among the five patients who were positive for EGFR 19del-T790M-cis-C797S mutations, and who received brigatinib and cetuximab combination therapy, three patients achieved partial response, and two had stable disease, resulting in an overall objective response rate of 60% and disease control rate of 100%. Among the 10 patients who were positive for EGFR 19del or L858R-T790M-cis-C797S mutations and received chemotherapy, only one patient achieved partial response, five had stable disease, and the other four did not benefit from chemotherapy, resulting in an overall objective response rate and disease control rate of 10% and 60%, respectively. The median progression-free survival of patients who received combined targeted therapy was 14 months, and 3 months for those treated with chemotherapy. No grade III to IV adverse events were observed in any patient.Conclusions: Our retrospective study provides clinical evidence that a combined targeted therapy of brigatinib and cetuximab could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients who acquire EGFR T790M-cis-C797S-mediated resistance to osimertinib. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.