Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective： To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer （NSCLC）. Methods： A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results： A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate （RR） was 36.0% （32/89）, and the disease control rate （DCR） was 69.7% （62/89）. RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma （P〈0.05）. The symptom improvement rate was 57.3% （51/89）, and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 （33.7%）] and diarrhea [15/89 （16.9%）]. The level of toxicity was typically low. Conclusions： The use of icofinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Icotinib hydrochloride对人涎腺腺样囊性癌细胞增殖的影响

分别应用0(对照组)、5、10、20、40、80μmol·L-1icotinib hydrochloride(盐酸埃克替尼)处理体外培养的人涎腺腺样囊性癌(ACC-M)细胞,形态学观察icotinib hydrochloride作用12、24、48、72、96 h后ACC-M细胞的生长状态变化.用四甲基偶氮唑盐法检测不同浓度的icotinib hydrochloride作用不同的时间下ACC-M细胞的增殖抑制率.结果显示,icotinib hydrochloride作用后ACC-M细胞体积变小,胞质皱缩,细胞间隙增大,胞内颗粒增多,贴壁细胞变圆、漂浮.Icotinib hydrochloride抑制ACC-M细胞增殖.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report

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.

Lung adenocarcinoma harboring rare epidermal growth factor receptor L858R and V834L mutations treated with icotinib:A case report

BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors,which bring uncertainty to clinical treatment.CASE SUMMARY A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain.Chest computed tomography revealed lung spaceoccupying lesions and multiple lymphadenectasis.Bronchoscopy and pathology suggested lung adenocarcinoma.Compound variation of EGFR gene(exon 21 L858 R/V834 L)was detected in both tissue and circulating tumor deoxyribonucleic acid samples.As a result of next-generation sequencing and her family’s wishes,the patient was given oral treatment with icotinib hydrochloride(125 mg/d,tid)from March 21,2019 and has achieved stable disease for the last 1 year.CONCLUSION Non-small cell lung adenocarcinoma with EGFR L858 R/V834 L was treated successfully with icotinib,and it may be a new medication treatment option.

Pharmacoeconomic Study on the Treatment of Terminal Non-small Cell Lung Cancer with Icotinib and Pemetrexed Combined with Cisplatin

Objective To provide theoretical basis for clinical treatment of patients with terminal non-small cell lung cancer through the analysis of the cost and adverse reactions of the joint treatment of icotinib and pemetrexed combined with cisplatin.Methods The clinical data of the patients diagnosed with terminal non-small cell lung cancer were collected and analyzed according to different drug administration schedules(n=53 of each group).The efficacy,cost and adverse reactions were evaluated respectively,aiming to provide the pharmacoeconomic evidence for the clinical applications.Results and Conclusion There was no significant difference between the efficacy of the icotinib group and the pemetrexed combined with cisplatin group,but the cost of the icotinib group was much lower,and the adverse reactions such as leukopenia,anemia,vomiting and nausea were far fewer than those in the pemetrexed combined cisplatin group.Although the two methods have similar therapeutic effects,the icotinib group has lower cost and fewer adverse reactions.Thus,from the perspective of pharmacoeconomics,icotinib has its advantage over the traditional regimen on the treatment of terminal non-small cell lung cancer.

紫龙金联合埃克替尼对Lewis肺癌荷瘤小鼠免疫功能及肿瘤血管生成的影响

目的:探讨紫龙金联合埃克替尼对Lewis肺癌荷瘤小鼠免疫功能及肿瘤血管生成的影响。方法:选用无特定病原体(SPF)级C57BL/6雄性小鼠50只,随机取10只用于制备Lewis瘤细胞悬液,余40只于其右前肢腋窝皮下分别接种0.2 mL的Lewis瘤细胞悬液,建立Lewis肺癌荷瘤小鼠模型,并将其随机均分为模型组、紫龙金组、埃克替尼组、联合观察组,每组10只。对比各组肿瘤重量、肿瘤生长抑制率;用酶联免疫吸附试验(ELISA)法检测小鼠血管内皮生长因子、小鼠肿瘤组织白细胞介素2(IL-2)、肿瘤坏死因子α(TNF-α)、干扰素(IFN-γ)水平;流式细胞术检测小鼠脾脏免疫细胞比例。结果:与紫龙金组及埃克替尼组比较,联合观察组小鼠的肿瘤重量和小鼠肿瘤生长抑制率高(均P<0.05),血管内皮生长因子水平及微血管密度低(均P<0.05),CD4^(+)T、CD8^(+)T及B淋巴细胞比例高(均P<0.05),肿瘤组织的IL-2、TNF-α、IFN-γ水平低(均P<0.05)。结论:紫龙金和埃克替尼联合治疗具有协同作用,显著降低了Lewis肺癌荷瘤小鼠模型的肿瘤重量,抑制了血管生成,增强了免疫功能,减轻了炎症反应。

Tumor gene mutations and messenger RNA expression： correlation with clinical response to icotinib hydrochloride in non-small cell lung cancer

Background Molecular targeted drugs is now widely used in non-small cell lung cancer （NSCLC） clinical treatment. Icotinib hydrochloride is a new type of oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （EGFR-TKIs）. In this study, we examined the role of EGFR, K-RAS, B-RAF somatic mutations and EGFR mRNA expression in tumor specimens from advanced NSCLC patients as predicators of the efficacy of icotinib hydrochloride. Methods We analyzed tumor paraffin-embedded specimens, which were obtained from 14 of 40 patients with advanced NSCLC who enrolled in the stage I clinical trial of icotinib hydrochloride. Somatic mutations were evaluated by mutant-enriched liquidchip （MEL） technology, and EGFR mRNA expression was measured by branched DNA liquidchip （MBL） technology. Results In the 14 specimens, seven patients showed EGFR mutations, exon 19 deletion （3/7） and exon 21 point mutation （4/7）; and two patients showed K-RAS mutation. No mutations in EGFR exon 20. or B-RAF were detected. In patients with EGFR mutation, one patient developed progress disease （PD）, three patients had stable disease （SD）, two patients had partial responses （PR） and one patient had a complete response （CR）. In patients with wild-type EGFR, four patients had PD, three patients acquired SD, and none had PR/CR （P=-0.0407）. EGFR mutations were associated with better progress-free survival （PFS） （141 days vs. 61 days） but without a statistically significant difference （P=0.8597）, and median overall survival （OS） （-〉449 days vs. 140 days）. EGFR mRNA expression levels were evaluated （three high, eight moderate, one low, and two that can not be measured due to insufficient tumor tissue） and no statistically significant relationships was observed with response, PFS or OS. Conclusions The EGFR mutation rate was consistent with that reported in the Asian population, so the MEL technology is reliable for measuring EGFR mutation with high throughput and rapidity. EGFR exon 19 deletions and exon 21 point mutation are predictive biomarkers for response to icotinib hvdrochloride as second line treatment or above.

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer

Background The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer （NSCLC） in a Chinese patient population. Methods This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib （100 to 400 mg）, administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity. Results Forty patients with stage IIIB （15%） or IV （85%） NSCLC were included in the study. They had mainly adenocarcinoma （85%）, with a performance status （PS） of 0 （45%） or 1 （55%） and less than half the patients （45%） had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash （25%）, diarrhea, nausea and abdominal distention. One definite interstitial lung disease （ILD） was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one （2.5%） patient receiving 150 mg gained complete response （CR） that persisted for 44 weeks, seven （17.50%） patients had partial remission （PR）, and 18 （45%） patients had stable disease （SD）. The objective response including CR＋PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks （range： 12 to 32 weeks）. The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed. Conclusions Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy

Background The preclinical experiments and several clinical studies showed icotinib,an oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor,in Chinese patients with advanced non-small cell lung cancer （NSCLC） who failed previous chemotherapy.We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.Methods The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1,2011 to July 31,2012 were retrospectively analyzed.All patients were given icotinib treatment after the failure of previous chemotherapy.Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.Results The objective response rate was 33/149 and disease control rate was 105/149.No complete response occurred.Median progression free survival （PFS） with icotinib treatment was 5.03 months （95％ CI：3.51 to 6.55）.Median overall survival was 12.3 months （95％ CI：10.68 to 13.92）.Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS.At least one drug related adverse event was observed in 65.8％ （98/149） of patients,but mostly grade 1 or 2 and reversible and none grade 4 toxicity.Conclusions lcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy.It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1

UDP-glucuronosyltransferase 1A1(UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug–drug interactions(DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The IC_(50) values of icotinib and erlotinib against UGT1A1-mediated NCHN-O-glucuronidation in human liver microsomes(HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with the Kivalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration–time curve(AUC) of NCHN. These findings are helpful for the medicinal chemists todesign and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risks via UGT1A1 inhibition.

埃克替尼联合培美曲塞治疗表皮生长因子受体敏感突变非小细胞肺癌的疗效分析

目的分析埃克替尼联合培美曲塞治疗表皮生长因子受体(EGFR)敏感突变非小细胞肺癌(NSCLC)的疗效。方法选取2018年1月—2021年7月广东医科大学附属医院收治的152例晚期NSCLC患者为研究对象,以随机数字表法分为对照组和实验组,各76例。对照组口服埃克替尼,125 mg/次,3次/d。实验组在对照组基础上静脉滴注培美曲塞500 mg/m2,每3周给药1次。两组患者持续用药至疾病进展或毒性不耐受。比较两组持续治疗3个疗程的抗肿瘤疗效、肿瘤标志物、肺功能、免疫功能、肝功能及药物安全性,统计两组患者1年生存情况。结果治疗期间共脱落3例。实验组疾病控制率高于对照组(P<0.05)。实验组治疗前后胸甘激酶-1、神经元烯醇化酶、癌胚抗原、用力肺活量、第1秒用力呼气容积/用力肺活量、Th1/Th2、Th17/Treg、CD4^(+)/CD8^(+)的差值均高于对照组(P<0.05)。两组治疗前后丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素的差值比较,差异均无统计学意义(P>0.05)。实验组、对照组总药物不良反应发生率分别为25.33%和21.62%,差异无统计学意义(P>0.05)。截至随访结束,两组各失访2例。实验组73例患者存活59例,对照组72例患者存活56例,两组1年生存曲线比较,差异无统计学意义(P<0.05)。结论埃克替尼联合培美曲塞治疗EGFR敏感突变NSCLC患者,可增强近期抗肿瘤疗效,抑制肿瘤标志物合成,改善肺功能及免疫功能,且安全性良好。

埃克替尼和吉非替尼靶向治疗晚期非小细胞肺癌的临床效果及结局分析

目的 分析埃克替尼和吉非替尼靶向治疗晚期非小细胞肺癌(NSCLC)的临床效果。方法 选取我院2018年4月至2021年4月收治的80例晚期NSCLC患者为研究对象,根据随机数字表法将其分为对照组(n=40,吉非替尼)和研究组(n=40,埃克替尼)。比较两组的治疗效果、血清指标、免疫功能、生存质量、治疗结局与不良反应发生情况。结果 两组的疾病控制率比较,差异无统计学意义(P>0.05)。治疗后,两组的癌胚抗原(CEA)、癌抗原125(CA125)、神经钙黏素mRNA、血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)水平均降低,且研究组低于对照组(P<0.05)。治疗后,研究组的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组(P<0.05)。治疗后,研究组的欧洲癌症研究与治疗组织生存质量核心量表(EORTC QLQ-C30)各维度评分高于对照组(P<0.05)。研究组的死亡率低于对照组(P<0.05);两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 埃克替尼靶向治疗晚期NSCLC能够取得不输于吉非替尼的临床效果,可改善血清指标,提升免疫功能,延长生存时间,提高生存质量。

阿帕替尼联合埃克替尼治疗EGFR基因21号外显子L858R突变型NSCLC的临床观察

目的探究对表皮生长因子受体(EGFR)基因21号外显子L858R突变型非小细胞肺癌(NSCLC)采用阿帕替尼联合埃克替尼治疗的临床效果。方法将EGFR基因21号外显子L858R突变型NSCLC患者101例按随机数表法分为观察组(n=51)与对照组(n=50)。观察组采用阿帕替尼联合埃克替尼治疗,对照组仅采用埃克替尼治疗,治疗时间为56 d,2个周期。比较2组近期疗效、不良反应,并采用K-M生存分析曲线图分析2组远期疗效。结果观察组与对照组的客观缓解率(ORR)(74.51%vs 74.00%)与疾病控制率(DCR)(92.16%vs 94.00%)差异均无统计学意义(P>0.05);治疗期间2组未出现2级以上不良反应,观察组高血压和蛋白尿发生率分别为52.94%、50.98%,分别高于对照组的16.00%、10.00%,差异有统计学意义(P<0.05)。观察组生存率显著高于对照组(69.3%vs 43.1%),差异有统计学意义(P<0.05)。结论EGFR基因21号外显子L858R突变型NSCLC采用阿帕替尼联合埃克替尼治疗,可延长患者的无进展生存时间,不良反应的发生可接受。

埃克替尼治疗晚期非小细胞肺癌患者的临床效果

目的分析埃克替尼治疗晚期非小细胞肺癌(NSCLC)患者的临床效果。方法选取2019年4月至2022年4月我院收治的80例晚期NSCLC患者为研究对象,根据随机数字表法将其分为对照组(n=40,吉非替尼)和研究组(n=40,埃克替尼)。比较两组的治疗效果。结果研究组的疾病控制率高于对照组,差异具有统计学意义(P<0.05)。治疗后,研究组的miR-185-5p、miR-204-5p高于对照组,Lemur酪氨酸激酶3(LMTK-3)、POK红系髓性致癌因子(Pokemon)水平低于对照组,差异具有统计学意义(P<0.05)。治疗后,研究组的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)优于对照组,差异具有统计学意义(P<0.05)。两组的并发症总发生率比较,差异无统计学意义(P>0.05)。研究组的体力状况优于对照组,差异具有统计学意义(P<0.05)。结论埃克替尼治疗晚期NSCLC患者的效果明显,可改善免疫指标及体力状况,更好地控制病情,改善预后,临床可进一步推广运用。

抗肿瘤药Icotinib hydrochloride

癌症是全世界首要的死因之一。据统计，2008年就有760万人死于癌症，其中有100万人死于肺癌，71％的肺癌死者是由于吸烟所致。表皮生长因子受体（EGFR）为受体酪氨酸激酶家族成员之一，其广泛表达于多种肿瘤（如乳腺癌、头颈癌和卵巢癌）中，故而成为抗癌治疗最具潜力的靶点之一。第1代EGFR抑制剂吉非替尼（gefitinib）和埃罗替尼（erlotinib）已获准用于经其他抗肿瘤药物治疗无效的晚期非小细胞肺癌（NSCLC）患者。该类药物的优点之一是避免了传统化疗药物所致的常见毒副作用（尤其是骨髓抑制）。然而，尽管该类药物的临床研究在一开始获得了成功，随后研究人员发现了一个问题，即EGFR抑制剂与以铂类药物为基础的化疗方案联用并不能有效改善生存期，

国家医保谈判对公立医院抗肿瘤药物采购费用、数量及结构的影响:以EGFR-TKI靶向药物为例

目的分析国家医保药品目录准入谈判(以下简称“国谈”)政策对某省公立三级医院非小细胞肺癌EGFRTKI靶向药物采购费用、数量及结构的影响,为相关政策制定提供依据。方法收集2018年1月—2020年12月某省公立三级医院EGFR-TKI靶向药物每月采购数据,利用中断时间序列模型分析采购费用、数量、药品结构及日均费用的变化趋势。结果阿法替尼、奥希替尼、吉非替尼、埃克替尼、厄洛替尼5种EGFR-TKI靶向药物总体采购量及费用以稳定为主,2018年国谈准入品种采购量及费用上升。5种EGFR-TKI靶向药物药品结构变化明显,呈即刻上升趋势;各品种日均费用出现不同程度的下降。结论国谈政策的实施增加了靶向药物的使用,国谈准入药物品种逐步进入临床,患者的用药负担进一步减轻。

盐酸埃克替尼联合安罗替尼一线治疗晚期非小细胞肺癌效果以及安全性分析

目的探究盐酸埃克替尼联合安罗替尼一线治疗晚期非小细胞肺癌(NSCLC)的效果与安全性。方法选取2018年1月至2019年9月在内蒙古医科大学附属医院接受一线治疗的100例晚期NSCLC患者,按照随机数字表法分为观察组和对照组,各50例。对照组口服盐酸埃克替尼治疗,观察组在对照组的基础上口服盐酸安罗替尼胶囊治疗。比较2组临床疗效、治疗前和治疗4个周期后健康相关生活质量(HRQol)、疾病相关症状以及体能状态评分,比较2组治疗期间不良事件发生率。结果治疗4个周期后,观察组客观缓解率、疾病控制率均高于对照组[72.0%(36/50)比52.0%(26/50)、82.0%(41/50)比64.0%(32/50)](均P<0.05)。治疗4个周期后,2组躯体、角色、认知、情绪、社会功能评分和整体生命质量评分及恶心呕吐、便秘、腹泻、经济困难症状评分均高于治疗前,疲乏、疼痛、气促、失眠、食欲丧失症状评分及东部肿瘤协作组评分为2分的患者比例均低于治疗前(均P<0.05)。2组治疗期间不良事件均为1~2级,组间各不良事件发生率比较差异均无统计学意义(均P>0.05)。观察组无进展生存期、缓解持续时间、总生存期均长于对照组,1年及2年的总生存率均高于对照组(均P<0.05)。结论盐酸埃克替尼联合安罗替尼一线治疗晚期NSCLC的效果好,可改善患者生活质量与相关症状,且安全性较好。

PD-L1失调介导了埃克替尼对EGFR突变晚期非小细胞肺癌的影响

目的利用表皮生长因子受体(epidermal growth factor receptor,EGFR)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞探究程序性细胞死亡配体1(programmed cell death ligand 1,PDL1)在埃克替尼抗性中的潜在作用。方法采用实时荧光定量PCR(qRT-PCR)和Western印迹检测A549、HCC827和PC-9细胞中p-EGFR和PD-L1的表达水平。MTT方法评估HCC827和PC-9细胞对埃克替尼的敏感性。采用PD-L1敲除来评估对埃克替尼敏感性的影响,并使用小鼠异形移植模型进行体内实验。结果与A549细胞比较,HCC827和PC-9细胞中p-EGFR和PD-L1水平较高。埃克替尼对HCC827和PC-9细胞增殖有显著的抑制作用,并激活细胞凋亡。敲除PD-L1显著降低了埃克替尼对HCC827和PC-9细胞的抑制作用。与sh-NC+埃克替尼组比较,PD-L1敲除在体内降低对埃克替尼的敏感性。结论埃克替尼对EGFR突变NSCLC细胞有抑制作用,PD-L1有助于EGFR突变NSCLC细胞对埃克替尼的敏感性。