The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

Both platinum-based doublet chemotherapy （PBC） and epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） prolong the survival of patients with advanced non-small cell lung cancer （NSCLC）. In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival （OS）. Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria： in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase Ill clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian （predominantly Caucasian） populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs （r = 0.797, P 〈 0.001）. The correlation was obvious in the trials in Asian populations （r= 0.936, P 〈 0.001） but was not statistically significant in the trials in predominantly Caucasian populations （r = 0.116, P = 0.588）. These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalJtJes available for therapy.     

靶向药物同步个体化放疗治疗晚期/转移性非小细胞肺癌的Ⅱ期临床研究

目的探索靶向药物吉非替尼或厄洛替尼同步个体化放疗治疗晚期/转移性非小细胞肺癌(NSCLC)的安全性和有效性,探索肿瘤综合治疗的新模式。方法 21例经病理组织学确诊的Ⅳ期NSCLC接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)吉非替尼或厄洛替尼同步胸部放疗。胸部放疗采用根治性为目的的适形放疗(CRT)和/或伽马射线立体定向放疗(γ-SBRT)。不良反应依据美国国立癌症研究院常见不良反应标准(NCI-CTCAE3.0)评价。主要研究终点为安全性,总生存(OS)和中位生存时间(MST)。次要研究终点为肿瘤局部控制率、肿瘤进展时间(TTP)、无进展生存(PFS)。结果吉非替尼或厄洛替尼同步个体化放疗的皮肤不良反应、消化道反应和血液学不良反应可控,没有导致严重的肺部不良反应。接受胸部放疗计划的患者中位肿瘤靶区容积(GTV)是55 cm~3(范围,5～420 cm~3),GTV边缘中位剂量是70Gy(范围,42～70Gy),中位生物等效剂量(BED)是105Gy(范围,60～119Gy)。EGFR-TKIs中位维持治疗时间是8.1个月(范围,1.9～29.0个月),EGFR-TKIs同步放疗没有发生治疗相关性死亡。中位随访10.0个月(范围,1.1～38.3个月),胸部肿瘤局部控制率为95%,中位TTP为5.8个月(范围,1.2～18.6个月),中位PFS为7.8个月(95%的可信区间,1.7～13.9个月),MST为21.8个月(95%的可信区间,5.3～38.4个月),1年PFS为39%,1年、2年和3年的OS分别为41%、24%和24%。结论靶向药物同步放疗安全有效,可以作为晚期/转移性NSCLC的治疗选择。     

益气养阴解毒方治疗肺癌患者EGFR-TKIs相关皮疹的临床观察

目的观察益气养阴解毒法治疗表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)相关皮疹的临床疗效;方法2016年1月—2019年9月于北京中医药大学东直门医院26例经病理确诊为肺腺癌,接受EGFR-TKIs治疗后出现皮疹的患者为治疗组;2016年1月—2019年9月于北京市东城区第一人民医院21例经病理确诊为肺腺癌,接受EGFR-TKIs治疗后出现皮疹的患者为对照组。治疗组予益气养阴解毒方口服,同时皮损部位应用本方外洗;治疗组皮损处外用百多邦莫匹罗星软膏。两组均以21 d为1个疗程,1个疗程后评价疗效。根据美国国家癌症研究所一不良事件公共术语标准4.0版(NCI-CTCAE 4.0)对皮肤毒性评级进行疗效评价;参考《中药新药临床研究指导原则》评价中医证候疗效;皮肤病生活质量指数(dermatology life quality index,DLQI)评价皮疹对患者生活质量的影响。结果一个疗程后,对照组及治疗组治疗前后比较,均出现不同程度改善,差异有统计学意义(P<0.05);治疗组优于对照组,差异有统计学意义(P<0.01);治疗组在中医证侯改善及生活质量方面优于对照组,差异有统计学意义(P<0.05)。结论益气养阴解毒方口服联合外洗对肺腺癌患者接受EGFR-TKIs治疗后出现的皮疹具有较好疗效,能减轻EGFR-TKIs引起的皮肤毒副反应。     

1例奥希替尼致神经毒性不良反应报道

1例EGFR 21外显子L858R错义突变的Ⅳ期肺腺癌患者服用埃克替尼16个月后疾病进展,基因检测结果为T790M突变。改用第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）奥希替尼治疗4个月后出现行为异常,6个月后返院复查脑部MRI示脑转移瘤较前减少并缩小,但出现脑白质疏松,后于外院就诊期间发生癫痫,经分析考虑为奥希替尼所致神经毒性。本文首次报道了奥希替尼的罕见神经毒副反应,旨在提醒临床使用奥希替尼须警惕神经毒性。     

第三代EGFR-TKIs治疗晚期非小细胞肺癌的耐药机制及应对策略研究进展

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）是具有EGFR基因敏感突变的晚期非小细胞肺癌（NSCLC）患者的一线治疗药物。第一、二代EGFR-TKIs可有效治疗EGFR敏感突变的NSCLC,EGFR第20号外显子的T790M突变是第一、二代EGFR-TKIs的主要耐药机制。以奥西替尼为代表的第三代EGFR-TKIs治疗耐药后出现T790M突变的患者疗效显著,给晚期肺癌患者带来更多的生存获益。然而第三代EGFR-TKIs仍不可避免地出现耐药。本文对第三代EGFR-TKIs治疗晚期NSCLC耐药机制及应对策略的研究进展进行综述。     

EGFR-TKIs肺癌靶向治疗耐药的研究进展:文献计量学与可视化分析

目的:分析1950-2021年Web of science、中国知网收录的表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKIs)耐药,研究进展、知识基础、研究热点及研究前沿,为未来开展EGFR-TKI...     

Origin of the T790M mutation and its impact on the clinical outcomes of patients with lung adenocarcinoma receiving EGFR-TKIs

Objective

Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis.

表皮生长因子受体酪氨酸激酶抑制剂在肺癌以外的应用进展

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKIs)主要用于晚期非小细胞肺癌的分子靶向治疗,随着EGFR-TKIs的越来越深入研究,发现EGFR及其配体参与了包括乳腺癌、胰腺癌等在内的不同人类癌症发病过程。因此,EGFR-TKIs的治疗对象也不再局限于晚期非小细胞肺癌,其对乳腺癌、胰腺癌、头颈癌、食管癌和宫颈癌等恶性肿瘤也有较好的抑制作用,并且与EGFR-TKIs联合用药往往比单独用药效果更好。该文讨论了EGFR-TKIs在治疗肺癌以外其他癌症的应用研究,以及EGFR-TKIs与其他药物联合治疗乳腺癌、胰腺癌等恶性肿瘤的潜在应用前景。     

EGFR基因靶向治疗非小细胞肺癌的研究进展

非小细胞肺癌(Non-small cell lung cancer,NSCLC)是现阶段临床发现的肺癌患者中发病率最高的一种类型,治疗手段匮乏,效果不甚理想,目前临床中研究热点是EGFR基因在NSCLC靶向治疗中的作用。表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)是基于EGFR基因作用而开发出来,用于治疗EGFR基因突变阳性的NSCLC患者。本文综述了EGFR基因靶向治疗非小细胞肺癌的研究进展。     

Fatigue with epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients: A meta-analysis of randomized controlled trials

We conducted this systematic review to fully investigate the fatigue of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in cancer patients. The approved and clinical used EGFR-TKIs were selected for the present meta-analysis. The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with EGFR-TKIs were retrieved and the systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published till July 2017. Eighteen randomized controlled trials and 14088 patients were included. The current analysis suggested that the use of EGFR-TKIs increased the risk of all-grade fatigue (1.26;95%CI, 1.17–1.36;p < 0.00001) and high-grade (≥grade 3) fatigue (1.47;95%CI, 1.22–1.78;p < 0.0001). On subgroup analysis, the RR of high-grade fatigue varies significantly according to drug type, cancer type, treatment line, and treatment duration. The available data suggested that the use of EGFR-TKIs is associated with a significantly increased risk of fatigue in cancer patients.