厄洛替尼治疗非小细胞肺癌脑转移初步分析

背景与目的 非小细胞肺癌(Non-small-cell lung cancer,NSCLC)脑转移较常见,预后不佳.厄洛替尼是一种表皮生长因子受体酪氨酸激酶抑制剂,多应用于治疗晚期NSCLC.本研究拟了解厄洛替尼治疗NSCLC脑转移的疗效、预后及其相关因素.方法 回顾性分析30例NSCLC脑转移患者的临床资料,所有患者均口服厄洛替尼150mg/d.直到疾病进展、死亡或发生不可耐受的副反应.结果 厄洛替尼对颅内病灶的疗效为部分缓解2例(6.7%).疾病稳定17例(56.7%).疾病控制率为63.4%,对全身病变的总体疗效为部分缓解2例(6.7%),疾病稳定5例(16.7%),疾病控制率为23.4%.年龄、性别、吸烟状况、病理类型、PS评分、脑转移数目、脑转移时间、化疗及脑部放疗与否、副反应等各亚组之间的疗效对比均未见有统计学差异.中位疾病进展时间2.4个月,中位生存期7.7个月,1年、2年生存率分别为38.4%和15.2%.单因素分析显示生存期与患者的PS评分、吸烟状况、是否进行过脑部放疗及化疔具有相关性,多因素分析则显示生存期仅与患者是否进行过脑部放疗具有相关性,与患者的吸烟状况接近有统计学意义.结论 厄洛替尼对NSCLC脑转移具有一定的疗效,接受过脑部放疗的患者具有较好的生存获益,非吸烟者的生存时间有好于吸烟者的趋势.厄洛替尼可以作为NSCLC脑转移的一种治疗选择.     

吉非替尼治疗非小细胞肺癌脑转移的临床研究

目的：分析吉非替尼治疗非小细胞肺癌脑转移的疗效、生活质量、预后及其相关因素。方法：对40例资料完整的非小细胞肺癌脑转移患者的临床特点、治疗效果、生活质量及生存时间进行回顾性分析。所有患者发生脑转移后均口服吉非替尼250 mg/天,直到病变进展或发生不可耐受的不良反应。结果：吉非替尼治疗非小细胞肺癌脑转移的颅内病灶的疗效疾病控制率为83%,颅内病变疾病控制率与病理类型具有相关性。全身病变的疾病控制率为78%,全身病变疾病控制率与患者的病理类型、PS评分、脑转移数目（单发或多发）、服药后出现皮疹与否具有相关性（P〈0.05）。全组患者中36例患者完成生活质量评价问卷,治疗8周后5种功能状态（躯体、角色、情感、认知、社会）和整体生活质量评分的均值显著增加,且差异均有显著性（P〈0.05）;2个全身症状（乏力、食欲不振）以及肺癌相关症状（呼吸困难、咳嗽、胸痛）评分的均值降低,其中乏力、呼吸困难、咳嗽的差异有显著性（P〈0.05）。本组患者的中位TTP 6个月,TTP与患者的PS评分具有相关性（P=0.000）与服药后是否有皮疹具有相关性（P=0.016）。中位生存期11个月,生存期与PS评分、服药后皮疹情况和脑转移数目具有相关性（P分别为0.000、0.000和0.016）。不良反应可耐受,主要表现为轻度皮疹和腹泻。结论：吉非替尼治疗肺癌脑转移有效,可以改善患者预后,且不良反应轻微。     

吉非替尼同步γ射线立体定向外科加全脑放疗治疗非小细胞肺癌脑转移瘤的临床研究

评价吉非替尼同步伽马射线立体定向外科加全脑放疗治疗非小细胞肺癌（NSCLC）脑转移瘤的作用和获益影响因素。方法:回顾性分析23例NSCLC脑转移瘤患者接受吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的疗效、疾病进展时间、总生存时间、预后影响因素及不良反应。结果:颅内病灶的疗效为:CR 2例,PR 16例,SD 3例,PD 2例,有效率78.3%（18/23）,疾病控制率91.3%（21/23）。全身病变的总体疗效为:CR 0例,PR 5例,SD 12例,PD 6例,有效率21.7%（5/23）,疾病控制率73.9%（17/23）。中位疾病进展时间为8.3个月,中位生存时间为12.8个月。单因素分析显示:KPS评分、肿瘤累及体积、病理类型、RPA分级为疾病进展时间预测因素（P均<0.05）;而KPS评分、肿瘤累及体积、RPA分级则是生存时间预测因素（P均<0.05）。吉非替尼不良反应主要为Ⅰ~Ⅱ度皮疹和腹泻,患者均可耐受。结论:吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的治疗NSCLC脑转移瘤,有效率和疾病控制率高,具有较长的中位疾病进展时间和生存时间,不良反应轻微,是一种很有价值的治疗方法。其中,KPS评分、肿瘤体积、病理类型（腺癌）、RPA分级是影响获益和生存的重要因素。      

吉非替尼治疗非小细胞肺癌脑转移的初步结果

背景与目的 吉非替尼是一种口服的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），是治疗晚期非小细胞肺癌（NSCLC）的有效靶向药物之一。本研究的目的是探讨吉非替尼治疗NSCLC脑转移的疗效和耐受性。方法 对18例资料完整的NSCLC脑转移患者的临床特点、治疗效果及生存时间进行了回顾性分析。所有患者发生脑转移后均口服吉非替尼250mg／天，直到病变进展或其他原因停药。其中12例患者做了脑部放疗（A组），另6例单纯服用吉非替尼（B组）。结果 吉非替尼治疗NSCLC脑转移的总有效率为27．8％，疾病控制率为88．9％（1例CR，4例PR，11例SD，2例PD）。未观察到疗效与性别、病理类型、吸烟、是否做过脑部放疗等临床特点有相关性。中位随访期6月（1～24月），两组患者生存的差异无统计学意义（P=0．192）。吉非替尼的不良反应可耐受，主要表现为轻度皮疹和腹泻。结论 吉非替尼治疗NSCLC脑转移有效，有必要进一步开展随机对照临床研究，以明确靶向治疗对脑转移的作用。     

非小细胞肺癌脑转移厄洛替尼和吉非替尼治疗临床比较

目的比较和评价厄洛替尼和吉非替尼靶向治疗非小细胞肺癌脑转移的疗效。方法回顾性分析2009-01-01-2012-11-25广州医科大学附属第一医院81例晚期NSCLC初诊有脑转移患者和111例晚期NSCLC初诊无脑转移患者,192例患者均为肺腺癌合并EGFR基因突变,分为吉非替尼和厄洛替尼治疗组,生存分析采用Kaplan-Meier法统计,组间生存率比较采用Log-rank检验。结果初诊有脑转移患者颅内病灶,客观有效率为45.68%(37/81),疾病控制率为90.12%(73/81)。吉非替尼、厄洛替尼治疗的无进展生存期(progression-free survival,PFS)分别为9.5和9.0个月,P=0.344;不同EGFR突变类型(19外显子序列缺失突变、21外显子突变)PFS比较分别为10.4和8.6个月,P=0.408。初诊无脑转移患者PFS分别为14.0和15.0个月,P=0.369;不同EGFR突变类型的PFS分别为14.0和15.0个月,P=0.408。结论厄洛替尼和吉非替尼一线治疗肺癌EGFR突变脑转移效果无显著性差异。     

吉非替尼与厄洛替尼治疗非小细胞肺癌脑转移的临床观察

目的 探讨吉非替尼与厄洛替尼治疗非小细胞肺癌脑转移的疗效。方法 回顾性分析67例EGFR突变阳性的肺腺癌脑转移患者的病历资料,患者均口服吉非替尼250 mg/天（吉非替尼组,n=38）或厄洛替尼150 mg/天（厄洛替尼组,n=29）,直至发生颅内病变进展、死亡或不可耐受的不良反应。疗效分析采用RECIST 1.1版标准,生存分析采用Kaplan-Meier法并行Log-rank检验。结果 全组颅内病变的有效率（RR）和疾病控制率（DCR）分别为44.8％和92.5％,吉非替尼组和厄洛替尼组分别为42.1％、92.1％和48.3％、93.1％（P=0.881）。颅外病变的RR和DCR分别为53.7％和95.5％,吉非替尼组和厄洛替尼组分别为52.6％、94.7％和55.2％、96.6％（P=0.932）。全组患者的中位无进展生存期（PFS）和总生存期（OS）分别为10.8个月和15.3个月,吉非替尼组和厄洛替尼组分别为10.6个月、14.8个月和11.7个月、15.7个月（P=0.720,P=0.569）。结论 吉非替尼和厄洛替尼对EGFR突变阳性的非小细胞肺癌脑转移具有较好的疗效,可以作为脑转移患者的治疗选择,两种药物在脑转移瘤的疗效及患者的预后等方面无差异。     

埃克替尼治疗非小细胞肺癌脑转移的回顾性研究

目的 探讨埃克替尼治疗非小细胞肺癌（NSCLC）脑转移的疗效及安全性。方法 回顾性分析31例采用埃克替尼治疗的NSCLC 脑转移患者的临床资料。所有患者均口服埃克替尼125mg,每天3次,直至疾病进展或出现不可耐受的不良反应,其中25例患者接受脑部放疗。结果 31例患者颅内病灶的有效率（RR）和疾病控制率（DCR）分别为25.8％和83.9％,全身病灶的RR和DCR分别为38.7％和87.1％。接受埃克替尼联合脑部放疗的患者在RR上优于接受埃克替尼单药治疗者,但差异无统计学意义（P＞0.05）。RR和DCR与年龄、性别、病理类型、PS评分、脑转移数目、埃克替尼治疗情况、脑部放疗及表皮生长因子受体（EGFR）突变状况均无关。全组中位无进展生存时间（PFS）为6.5个月（95％CI：4.787～8.213个月）,其中EGFR突变型为10.1个月。PFS与EGFR 基因突变状况有关,而与其他临床病理特征无关。主要不良反应为皮疹、皮肤干燥和腹泻,以1～2级为主。结论 埃克替尼对NSCLC 脑转移有一定疗效,且不良反应可耐受,值得进一步研究。     

吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究

目的：观察吉非替尼与培美曲塞二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）情况,比较二者对晚期NSCLC患者的治疗效果、安全性的影响。方法将一线化疗治疗失败后的105例晚期NSCLC患者,随机分为吉非替尼组和培美曲塞组,分别接受吉非替尼与培美曲塞二线治疗,比较两组患者的治疗效果和安全性。结果近期疗效比较结果显示,吉非替尼组和培美曲塞组客观有效率（ORR）分别为24.0%和29.1%（P=0.987）,疾病控制率（DCR）分别为64.0%和70.9%（P=0.776）;吉非替尼组和培美曲塞组中位无进展生存时间（PFS）分别为5.2个月和4.1个月（P=0.026）,中位总生存期（OS）分别为7.9个月和6.7个月（P=0.031）,吉非替尼组PFS和OS均优于培美曲塞组。吉非替尼组的不良反应主要为非血液学毒性,培美曲塞组的主要不良反应为血液学毒性。结论吉非替尼及培美曲塞均可用于晚期NSCLC患者的二线治疗,疗效相当,但二者的不良反应各异,可根据患者的个体差异择优选用。     

晚期非小细胞肺癌吉非替尼二线和三线治疗的疗效比较

目的:探讨吉非替尼用于晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)二线或三线治疗对患者生存期的影响。方法:回顾性分析106例晚期NSCLC患者的病历和随访资料,其中62例患者接受吉非替尼二线治疗,44例患者接受吉非替尼三线治疗。应用Kaplan-Meier法进行生存分析。结果:两组患者的性别(P=0.51)、年龄(P=0.91)、体能状况评分(P=0.42)、临床分期(P=0.18)、吸烟史(P=0.95)和病理类型(P=0.99)的差异无统计学意义。吉非替尼二线治疗和三线治疗患者的中位无进展生存期分别分别为2.9和3.2个月(P=0.757),有效率分别为17.7%和11.4%(P=0.665),疾病控制率分别为48.4%和54.5%(P=0.822)。吉非替尼二线治疗和三线治疗患者的中位总生存期分别为24.0和21.0个月(P=0.524)。二线治疗获得疾病控制的30例患者以及三线治疗获得疾病控制的24例患者的中位总生存期分别为29.7和22.2个月(P=0.611)。吉非替尼二线治疗与三线治疗的不良反应相似。结论:吉非替尼用于晚期NSCLC二线治疗和三线治疗的缓解率和生存获益无明显差异。     

吉非替尼治疗晚期非小细胞肺癌脑转移的疗效

目的探讨吉非替尼治疗非小细胞肺癌(NSCLC)脑转移的疗效及其对预后的影响。方法44例NSCLC脑转移患者中,接受过全脑放疗者30例,接受过化疗者42例,均在入组前1个月结束治疗。入组者口服吉非替尼250 mg,每日1次,服药至疾病进展或死亡。服药后定期复查。结果吉非替尼治疗的有效率为31.8%,稳定率为47.7%,临床获益率为79.5%。中位无进展生存时间为9个月,中位总生存时间为13个月。吉非替尼对颅内转移灶的控制率达81.9%。既往接受全脑放疗患者与未接受全脑放疗者相比,其转移灶控制率差异无统计学意义(P=0.566)。结论吉非替尼治疗NSCLC脑转移的疗效显著,不良反应轻微,能明显改善患者预后,是晚期NSCLC患者的治疗方法之一。     

Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases.

PURPOSE: The purpose is to identify biological markers that predict brain metastasis and treatment outcome in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Samples were obtained from the primary tumors, lymph nodes, and brain metastases of 29 patients with NSCLC who had undergone resection of both the pulmonary tumors and the brain lesions. Samples from 29 patients matched for age, sex, and histology whose pulmonary tumors were resected served as controls. Samples were stained with H&E as well as immunohistochemical stains for epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX-2), and BAX. Comparisons were made between patients with and without brain metastasis. Independent investigators determined the percentage of positive cells. RESULTS: There was positive correlation in expression of all three biomarkers between primary lung tumors and lymph node metastases. Significantly higher levels of EGFR were found in lymph node metastases in the control group (P = 0.0147). COX-2 expression in brain lesions correlated with expression in primary tumors (P = 0.023). BAX levels were lower in poorly differentiated tumors in lymph node metastases in the control group (P = 0.01) and in brain metastases (P = 0.045). Low EGFR expression and high COX-2 expression in lymph node metastasis were associated with poorer treatment outcome. CONCLUSIONS: Expression of EGFR, COX-2, and BAX in primary lung tumors did not differ between patients with brain metastases from NSCLC and those without brain metastases. These three biomarkers cannot be used to predict brain metastasis. Studies of other biomarkers are under way in an effort to predict brain metastasis among patients with NSCLC.     

非小细胞肺癌脑转移患者放疗后的生存状况及预后分析

目的:探讨非小细胞肺癌脑转移放疗后生存状况及预后的相关因素。方法:回顾性分析本院2004年9月-2007年12月58例非小细胞肺癌脑转移患者的临床资料,Kaplan Meier法进行生存率统计,并进行Log-rank时序检验,利用比例风险模型(Cox模型)进行多因素分析,筛选相关因素。结果:非小细胞肺癌脑转移患者放疗后的1年生存率为37.9%,2年生存率13.8%。单因素分析结果显示,患者的KPS评分、脑转移数目、有无颅外转移、原发病灶控制情况及放疗方法对生存期有影响(P<0.05),多因素分析显示,KPS评分、脑转移灶数目是预后的独立因素(P<0.05)。结论:患者的KPS评分、脑转移灶数目、原发病灶控制情况、有无颅外转移及放疗方式是非小细胞肺癌脑转移的预后因素。KPS≥70分,脑转移灶为单发是肺癌脑转移患者良好的独立预后因素,这些患者的生存期较长,是潜在的治疗获益者。     

Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer

BACKGROUND: Brain metastases develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of chemotherapy for patients with brain metastases from NSCLC. METHODS: We analyzed 30 patients who were discovered to have brain metastases during the diagnosis of 121 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide and irinotecan with rhG-CSF support. Response in the brain lesions was evaluated by contrast-enhanced MRI scans after at least two courses. RESULTS: Fourteen patients achieved a partial response (PR) but there was no change (NC) in 13 patients and progressive disease (PD) in 1. Among patients with extracranial lesions, 18 had a PR and 11 had NC. The response rate in brain metastases was 50.0%, and that in extracranial primary and metastatic lesions was 62.1%. The median duration of response for intra- and extracranial lesions was 140 and 147 days, respectively. After completing chemotherapy, Gamma Knife radiosurgery was performed on 2 patients in remission and 8 patients at disease progression. The median survival time and 1-year survival rate were 382 days and 56.1%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with brain metastases from NSCLC.     

非小细胞肺癌脑转移患者接受一代表皮生长因子受体酪氨酸激酶抑制剂治疗的临床研究

背景与目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移患者接受一代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)的生存数据及影响因素未完全阐明.本研究对存在脑转移的NSCLC患者的生存数据进行分析,以期为指导临床实践提供一定的研究证据.方法 回顾性收集上海交通大学附属胸科医院2012年-2013年确诊肺癌脑转移并接受一代EGFR-TKIs治疗的病例.采用Kaplan-Meier单因素、Cox多因素分析方法,探讨NSCLC脑转移患者接受EGFR-TKIs的生存情况及影响因素.结果 总体人群中位无进展生存时间(progression-free survival,PFS)为10.0个月(95%CI:8.3-11.7),中位生存时间(overall survival,OS)为28.0个月(95%CI:22.9-33.1).病理组织类型、肿瘤分化程度分别是患者接受EGFR-TKIs后PFS、OS的独立影响因素(P分别为0.001、0.050).结论 NSCLC脑转移患者接受一代EGFR-TKIs具有良好的疗效,腺癌亚型患者的PFS长于非腺癌患者,其他肿瘤分化程度患者的OS长于肿瘤低分化患者.     

Prognostic Factors in Patients with Non-small Cell Lung Carcinoma and Brain Metastases: a Malaysian Perspective

Background: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma(NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used butincreasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotacticradiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomesin NSCLC patients receiving local therapy for brain metastases. Materials and Methods: The case records of 125patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres fromJanuary 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patientsreceiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariatetesting. Results: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients withmultiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure(yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgeryor SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use ofpost-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All fourfactors remained statistically significant on multivariate analysis. Conclusions: ECOG ≤2, presence of seizures,oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapysystemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.     

Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic

BackgroundBrain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC.MethodsWe reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models.ResultsAlthough limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8⁺ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion.ConclusionsDiscordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.     

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.     

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407

IntroductionThis exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone.MethodsWe pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189 and KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for 2 or more weeks (≥4 wk in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use at least 3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain.ResultsA total of 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab + chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% confidence interval (CI): 0.32‒0.70] and 0.63 [95% CI: 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI: 0.31‒0.62] and 0.55 [95% CI: 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without.ConclusionsWith or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all programmed death ligand 1 subgroups, including patients with programmed death ligand 1 tumor proportion score less than 1% and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naive patients with advanced NSCLC, including patients with stable brain metastases.     

The use of recursive partitioning analysis grouping in patients with brain metastases from non-small-cell lung cancer

BACKGROUND: This study evaluates the use of recursive partitioning analysis (RPA) grouping in an attempt to predict the survival probabilities in patients with brain metastases from non-small-cell lung cancer (NSCLC). METHODS: Seventy-two patients with brain metastases from NSCLC treated with radiation therapy were included in the study. Sixty-three patients were male and nine patients were female. Their median age was 57 years and their median Karnofsky performance status was 70. At the time of brain metastases, there was no evidence of the intrathoracic disease in 27 patients and the extrathoracic disease was limited to the intracranial disease in 42 patients. In accordance with RPA grouping, 12 patients were in Group 1, 24 patients were in Group 2, and 36 patients were in Group 3. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in 10 fractions in most of the patients. RESULTS: The median survival time was 7 months for Group 1, 5 months for Group 2 and 3 months for Group 3. The survival probability at 1 year was 50% for Group 1, 26% for Group 2 and 14% for Group 3. CONCLUSIONS: This study presents evidence supporting the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from NSCLC.     

甲磺酸奥希替尼治疗EGFR基因突变型非小细胞肺癌脑转移的疗效评价

目的:探讨甲磺酸奥希替尼治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变型非小细胞肺癌(non-small-cell lung cancer,NSCLC)脑转移的临床效果及预后因素.方法:回顾分析2017年5月-2019年12月60 例由蚌埠医学院第一附属医院肿...