Osimertinib as a Potential Targeted Therapy for Non-Small Cell Lung Carcinoma (NSCLC) Patients with EGFR Exon 20 T790M

Nur Zam Zam, Harun Iskandar, Nur Ahmad Tabri, Arif Santoso, Nurjannah Lihawa, Harry Akza Putrawan, Ferry Sandra
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Abstract

BACKGROUND: Emergence of drug resistance due to epidermal growth factor receptor (EGFR) Exon 20 T790M poses a challenge in the effective management of non-small cell lung carcinoma (NSCLC). Significant breakthrough in the management of NSCLC with a specific genetic alteration causes substantial condition improvement in patients whose cancer progressed after first-generation tyrosine kinase inhibitor treatment and who developed tumors with EGFR Exon 20 T790M mutation. The present study analyzed a cohort of NSCLC patients and investigated the incidence of the EGFR Exon 20 T790M status with Osimertinib therapy, along with its impact on survival rates.METHODS: This was a retrospective cohort study on 22 NSCLC subjects who were genetically examined for EGFR status from plasmic cell free total nucleic acid. Subjects with EGFR Exon 20 T790M mutation were treated with/without Osimertinib. Demographic and clinical data were descriptively summarized, and the differences of each variable and correlation between survival rate and EGFR Exon 20 T790M were analyzed.RESULTS: Subjects with (n=13) and without (n=9) EGFR Exon 20 T790M had survival rates of 10.77±2.45 and 4.78±1.48, respectively (p=0.000). Based on 1-year survival status of subjects with EGFR Exon 20 T790M, there were 3 Osimertinib-treated survivors and 2 Osimertinib-treated non-survivors. Eight subjects with EGFR Exon 20 T790M and without Osimertinib treatment did not survive (p=0.001).CONCLUSION: Since the treatment of Osimertinib demonstrated a noteworthy survival rate among NSCLC subjects with EGFR Exon 20 T790M, thus Osimertinib could be suggested as a potential targeted therapy for NSCLC subjects with EGFR Exon 20 T790M.KEYWORDS: non-small cell lung carcinoma, EGFR, Exon 20, T790M, osimertinib
奥西替尼作为EGFR外显子20t790m的非小细胞肺癌(NSCLC)患者的潜在靶向治疗
背景:表皮生长因子受体(EGFR)外显子20 T790M耐药的出现对非小细胞肺癌(NSCLC)的有效治疗提出了挑战。具有特定基因改变的NSCLC治疗取得重大突破,使第一代酪氨酸激酶抑制剂治疗后癌症进展并发展为EGFR外显子20 T790M突变的肿瘤患者的病情得到实质性改善。本研究分析了一组NSCLC患者,研究了奥西替尼治疗下EGFR外显子20 T790M的发生率及其对生存率的影响。方法:这是一项回顾性队列研究,对22名非小细胞肺癌患者进行了质细胞游离总核酸基因检测EGFR状态。EGFR外显子20 T790M突变的受试者使用/不使用奥西替尼治疗。描述性总结人口学和临床资料,分析各变量的差异及生存率与EGFR外显子20 T790M的相关性。结果:有EGFR外显子20t790m (n=13)和没有EGFR外显子20t790m (n=9)的患者生存率分别为10.77±2.45和4.78±1.48 (p=0.000)。根据EGFR外显子20 T790M患者1年的生存状态,有3名接受奥西替尼治疗的幸存者和2名接受奥西替尼治疗的非幸存者。8名EGFR外显子20 T790M且未接受奥西替尼治疗的受试者没有存活(p=0.001)。结论:由于奥西替尼治疗EGFR外显子20 T790M的NSCLC患者具有显著的生存率,因此可以建议奥西替尼作为EGFR外显子20 T790M的NSCLC患者的潜在靶向治疗药物。关键词:非小细胞肺癌,EGFR,外显子20,T790M,奥西替尼
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