Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.
Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.
Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years. 相似文献
BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging.CASE SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects.CONCLUSION This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases. 相似文献
目的:探讨埃克替尼治疗33例非小细胞肺癌( non small cell lung cancer,NSCLC )患者的疗效及安全性。方法对33例患者的临床特点、治疗效果、不良反应及生存时间进行了回顾性分析。所有患者均口服埃克替尼125 mg,3次/d,直到病变进展或不能耐受。结果 KPS评分升高率为21.2%(7例),埃克替尼总有效率24.2%,疾病控制率87.9%。中位生存时间10.2个月,1年生存率42.4%。脑转移患者的有效率明显高于无脑转移的患者。腺癌、无脑转移、KPS评分高的患者的生存时间优于其他病理类型、有脑转移、KPS评分低的患者。埃克替尼的不良反应主要表现为轻度皮疹、皮肤干燥、腹泻。结论埃克替尼治疗晚期NSCLC具有较好的疗效及安全性。 相似文献
Introduction: EGFR has been implicated in various malignancies such as NSCLC, breast, head and neck, and pancreatic cancer. Numerous drugs have been developed in order to target the tyrosine domain of EGFR as an approach in cancer treatment.Areas covered: This article focuses on the different generations of EGFR tyrosine kinase inhibitors (TKIs). This spans from the emergence of the first-generation EGFR-TKIs to overcoming drug resistance using second-generation EGFR-TKIs and to reducing adverse effect (AE) using mutant-selective third-generation EGFR-TKIs.Expert opinion: Current TKI treatment is frequently accompanied by drug resistance and/or serious AEs. There has been the promise of advancements in second-generation EGFR-TKIs that could overcome drug resistance, acting as second- or third-line salvage treatment, but this promise has yet to be met. That being said, both issues are currently being addressed with mutant-selective EGFR-TKIs with the expectation of bringing more EGFR-targeted therapy into the next phase of cancer therapy in the future. 相似文献
目的:观察埃克替尼治疗复治表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的晚期肺腺癌患者的疗效及不良反应。方法:收集2011年11月至2016年7月期间一线或多线化疗进展的98例EGFR 敏感突变的晚期肺腺癌患者应用埃克替尼治疗的疗效、不良反应及生存资料。结果:98例既往化疗失败的EGFR基因敏感突变晚期肺腺癌患者中,达到完全缓解(CR)1例(1.0%),部分缓解(PR)66例(67.3%),疾病稳定(SD)20例(20.4%),疾病进展(PD)11例(11.2%);客观缓解率(ORR)为68.4%(67/98),疾病控制率(DCR)为88.8%(87/98),中位无进展时间(mPFS)为8.8个月(95%CI:7.1~10.5个月),中位生存时间(mOS)为15.5个月(95%CI:11.8~19.2个月)。亚组分析中,19外显子缺失突变患者的ORR(82.0% vs 54.2%,P=0.003)、mPFS(11.0个月 vs 6.0个月,P=0.008)及mOS(20.0个月 vs 12.6个月,P=0.016)均优于21外显子L858R突变患者;非脑转移患者的mOS优于脑转移患者(16.0个月 vs 8.0个月,P=0.039);不吸烟患者的ORR 优于吸烟患者(76.7% vs 55.3%,P=0.023);不同性别、年龄、肺癌分期、治疗线数、转移器官数对预后的影响均未见差异有统计学意义。不良反应以皮疹、腹泻、肝功能异常为主,经对症处理后症状均可明显缓解。结论:埃克替尼治疗既往化疗失败的EGFR突变阳性的晚期肺腺癌患者取得了确切的疗效,且不良反应发生率低。 相似文献