The therapeutic features of EGFR L858R exon 21 mutation in non-small cell lung cancer

M. O. Mandrina, T. D. Barbolina, L. Y. Vladimirova, A. Storozhakova, K. Laktionov
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Abstract

Introduction. Monotherapy with EGFR tyrosine kinase inhibitors (TKIs) results in a worse prognosis for patients with the exon 21 L858R mutation than for patients with exon 19 Del. Thus, the search for alternative drug strategies that improve treatment outcomes for patients with NSCLC with the L858R mutation is an urgent problem. This article presents preliminary results of a pilot study of the effectiveness of chemotherapy integrated into targeted anti-EGFR therapy for patients with non-small cell lung cancer (NSCLC) with a mutation in exon 21 of the EGFR gene.Aim. To improve progression-free survival results on first-line therapy in patients with NSCLC with the L858R mutation.Materials and methods. From 2015 to 2021 23 patients were included in the study with advanced L858R 21 exon mutation NSCLC for the first line of treatment. Patients received TKI therapy for the first 2 months, followed by discontinuation of targeted therapy and receiving 3 courses of paclitaxel and carboplatin. Target therapy was then resumed until disease progression. The follow up period was 36 months.Results. The objective response rate (ORR) was 59.1%. Median progression-free survival 23 months [95% CI: 16–36]. Four (18.1%) patients developed grade 3-4 toxicity during chemotherapy, and therefore the 3rd course of chemotherapy was canceled in one patient. Due to toxicity during targeted therapy, gefitinib dose was reduced in one patient and the drug was changed from gefitinib to afatinib in the other one patient.Conclusion. Preliminary results of our study showed that integrating chemotherapy into targeted treatment for this category of patients may become a new worthy option to increase median PFS.
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非小细胞肺癌表皮生长因子受体 L858R 21 号外显子突变的治疗特点
简介。表皮生长因子受体酪氨酸激酶抑制剂(TKIs)单药治疗会导致外显子21 L858R突变患者的预后比外显子19 Del患者更差。因此,寻找能改善L858R突变NSCLC患者治疗效果的替代药物策略是一个亟待解决的问题。本文介绍了一项试点研究的初步结果,该研究针对表皮生长因子受体(EGFR)基因第21外显子突变的非小细胞肺癌(NSCLC)患者,探讨了化疗与抗EGFR靶向治疗相结合的有效性。提高L858R基因突变的NSCLC患者一线治疗的无进展生存率。2015年至2021年,23名晚期L858R 21外显子突变NSCLC患者被纳入一线治疗研究。患者在头2个月接受TKI治疗,随后停止靶向治疗,接受3个疗程的紫杉醇和卡铂治疗。然后恢复靶向治疗,直至疾病进展。随访期为36个月。客观反应率(ORR)为59.1%。无进展生存期中位数为23个月[95% CI:16-36]。4名患者(18.1%)在化疗期间出现了3-4级毒性,因此1名患者取消了第3个疗程的化疗。由于靶向治疗期间出现毒性,一名患者减少了吉非替尼的剂量,另一名患者的药物从吉非替尼改为阿法替尼。我们研究的初步结果表明,对这类患者将化疗纳入靶向治疗可能成为提高中位生存期的一个新的值得选择的方案。
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