Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer

Objective: Brigatinib, ceritinib, and alectinib are approved to treat crizotinib-refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), but no trial has compared them head-to-head. A matching-adjusted indirect comparison (MAIC) was conducted to estimate the relative efficacy of these agents in the crizotinib-refractory setting.

Methods: MAIC is a propensity score-type method that adjusts for differences in baseline characteristics between trials to estimate relative efficacy. Analyses were based on patient-level data from the ALTA trial for brigatinib and published summary-level trial data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for alectinib. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared.

Results: After matching, all key baseline characteristics were balanced between trials. Compared with ceritinib, brigatinib was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio (HR) [95% confidence interval]?=?0.38 [0.26–0.57]; ASCEND-2: median?=?18.3 vs 7.2 months, HR?=?0.33 [0.20–0.56]) and OS (ASCEND-1: not available; ASCEND-2: median 27.6 vs 14.9 months, HR?=?0.33 [0.17–0.63]). Versus alectinib, brigatinib was associated with longer PFS (NP28761: median?=?17.6 vs 8.2 months, HR?=?0.56 [0.36–0.86]; NP28673: median?=?17.6 vs 8.9 months, HR?=?0.61 [0.40–0.93]); results for OS were inconclusive (NP28761: median?=?27.6 vs 22.7 months, HR?=?0.70 [0.42–1.16]; NP28673: median?=?27.6 vs 26.0 months, HR?=?0.66 [0.39–1.09]). ORR was similar.

Conclusion: In crizotinib-refractory ALK?+?NSCLC patients, relative efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib and prolonged PFS vs alectinib.     

Ceritinib for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer

Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment of human cancer. Several oncogenic druggable alterations have been so far identified, with anaplastic lymphoma kinase (ALK) gene rearrangements representing one of the newest and most appealing. Crizotinib is now recognized as the standard of care in ALK-positive NSCLC due to the positive results of recently published trials. Unfortunately, resistance inevitably occurs within the first year of treatment. Overcoming resistance is the major challenge in clinical oncology, and novel potent ALK inhibitors are currently under evaluation, including ceritinib. Ceritinib is an oral, potent, second-generation ALK inhibitor demonstrating activity in patients who develop resistance to crizotinib. Recent data also suggested efficacy in ALK-inhibitor-naive population, thus supporting investigation of the drug in front-line setting.     

克唑替尼联合紫杉醇和顺铂治疗ALK阳性非小细胞肺癌的疗效观察

目的探究克唑替尼联合紫杉醇和顺铂治疗间变淋巴瘤激酶(ALK)阳性非小细胞肺癌(NSCLC)的临床疗效。方法选取2012年1月—2014年3月在榆林市第一医院接受治疗的ALK阳性NSCLC患者67例,随机分为对照组(33例)和治疗组(34例)。对照组静脉滴注紫杉醇注射液175 mg/m2,1次/d;并于停药30 min后静脉滴注顺铂注射液75 mg/m2,1次/d。治疗组在对照组基础上口服克唑替尼胶囊,1粒/次,2粒/d。两组均治疗2个月,并随访24个月。观察两组的临床疗效,比较两组的血清肿瘤标志物、不良反应和生存率。结果治疗后,对照组和治疗组的有效率分别为27.27%、61.76%,两组比较差异有统计学意义(P0.05)。治疗后,两组癌胚抗原(CEA)、糖类抗原(CA125)和细胞角蛋白19片段(CYFRA21-1)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05、0.01);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。随访后,对照组和治疗组的死亡率分别为24.24%、14.71%,中位无进展生存期(PFS)分别为13、17个月,两组比较差异有统计学意义(P0.05)。结论克唑替尼联合紫杉醇和顺铂治疗ALK阳性NSCLC具有较好的临床疗效,可降低血清肿瘤标志物水平,延长中位PFS,提高患者的生存率,具有一定的临床推广应用价值。     

Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials

Abstract

Objective:

Nilotinib and dasatinib have not been directly compared in a randomized trial for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). The purpose of this study was to indirectly compare rates of major molecular response (MMR), progression-free survival (PFS) and overall survival by month 12 with nilotinib and dasatinib treatment of newly diagnosed CML-CP.     

An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer

Abstract

Objective:

There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology.     

Crizotinib: in locally advanced or metastatic non-small cell lung cancer

Crizotinib is an inhibitor of receptor tyrosine kinases (including anaplastic lymphoma kinase [ALK]). Oral crizotinib 250 mg twice daily was associated with clinically meaningful response rates in two noncomparative trials (phase I and phase II) in patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC). In the phase I trial (median duration of treatment of 32 weeks) and phase II trial (median duration of treatment of 22 weeks), the objective response rate in crizotinib recipients was 61% and 50%, respectively, and the median duration of response was 48.1 and 41.9 weeks, respectively. Responses were rapid, with the majority of patients achieving an objective response within the first 8 weeks of treatment. Crizotinib was generally well tolerated, with most adverse reactions being grade 1 or 2. The most commonly reported treatment-related adverse reactions were vision disorder, gastrointestinal disorders and oedema.     

达可替尼对比吉非替尼一线治疗EGFR突变晚期或转移性非小细胞肺癌的成本效果分析

目的 比较达可替尼和吉非替尼一线治疗中国表皮生长因子受体(EGFR)突变晚期或转移性非小细胞肺癌(NSCLC)的成本效果.方法 建立无疾病进展、疾病进展和死亡三种健康状态的分区生存模型.基于ARCHER 1050临床试验获取转移概率和安全性数据,根据已发表文献获得健康效用值,从卫生服务体系角度只考虑直接医疗成本,包括药...     

泽菲联合顺铂治疗中晚期非小细胞肺癌近期疗效观察

目的评价泽菲(吉西他滨,GEM)联合顺铂(DDP)(GP方案)对中晚期非小细胞肺癌(NSCLC)的疗效、临床受益情况和毒副作用。方法42例中晚期非小细胞肺癌,初治31例,复治11例,以GP方案化疗,每例持续2～3个周期,共102个周期。结果42例化疗患者,有效率(CR+PR)达52.4%(22/42),稳定(SD)者占35.7(15/42)%,进展(PD)者占11.9%(5/42)。毒副反应:Ⅲ～Ⅳ度白细胞减少者为30.9%,Ⅲ～Ⅳ度血小板减少者为14.2%,Ⅲ～Ⅳ度血红蛋白降低者为11.9%。结论GEM联合DDP治疗中晚期非小细胞肺癌有较好疗效,毒副反应轻,易耐受。     

吉非替尼门诊治疗晚期非小细胞肺癌疗效观察

目的:评价吉非替尼门诊治疗晚期非小细胞肺癌的疗效及毒副反应。方法:对72例化疗失败或不能耐受化疗及不愿接受化疗的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250 mg,口服,qd,至病情进展或出现不可耐受的不良反应。结果:72例患者中无完全缓解患者,部分缓解25例(34.7%),稳定18例(25.0%),疾病控制率59.7%,进展29例(40.3%)。中位肿瘤进展时间(TTP)为7.0个月,1年生存率为52.7%。与药物相关的不良反应依次为痤疮样皮疹34例(47.2%),皮肤干燥21例(29.2%),腹泻19例(26.4%),恶心9例(12.5%),肝功能异常(ALT,AST升高)3例(4.2%)。结论:吉非替尼门诊治疗晚期NSCLC安全有效,毒副反应轻微,患者耐受性和依从性好。     

吉非替尼治疗晚期复发非小细胞肺癌

目的 评价吉非替尼治疗晚期复发非小细胞肺癌的临床价值.方法 48例经病理确诊既往化疗失败的NSCLC患者,吉非替尼250mg口服,每日1次,连续用药至肿瘤进展或发生不可耐受的毒副作用.结果 48例均可评价疗效,总RR为22.9%,腺癌患者的有效率显著高于非腺癌患者(P=0.024),不吸烟者的有效率显著高于吸烟者(P=0.011),疾病控制率77.1%,中位PFS为4个月,中位生存期为8.9个月,常见的毒副作用是皮疹和腹泻.结论 吉非替尼治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性.     

恩度联合NP或GP方案一线治疗晚期非小细胞肺癌疗效比较

目的研究恩度联合不同标准含铂化疗方案一线治疗晚期非小细胞肺癌的疗效差异。方法晚期非小细胞肺癌患者分别接受恩度联合标准NP/NC(长春瑞滨+顺铂/卡铂)或GP/GC(吉西他滨+顺铂/卡铂)方案化疗,恩度于化疗周期第1～14 d使用,每天15mg。观察两组患者的客观缓解率、无进展生存期、总生存期等疗效指标有无差异。结果共有35例患者参与了该项临床研究,NP/NC组14例,GP/GC组21例。两组患者的客观缓解率分别为21.4%和14.3%(P=0.664),疾病控制率为78.6%和90.5%(P=0.369);中位无进展生存期分别为13.3个月和12.4个月(P=0.720),中位总生存期分别为21.8个月和24.4个月(P=0.811),各项临床疗效评价指标的差异均无统计学意义。亚组分析显示不同病理亚型、性别、年龄的亚组近期疗效及生存期也均无显著差异。结论恩度联合标准含铂方案一线治疗晚期NSCLC疗效和生存相似,对化疗方案似乎没有选择性。     

培美曲塞联合顺铂一线治疗晚期非小细胞肺癌

目的观察培美曲塞联合顺铂一线治疗晚期非小细胞肺癌的近期疗效及安全性。方法对32例经病理组织学或细胞学检查确诊的晚期非小细胞肺癌初治患者进行培美曲塞联合顺铂化疗。培美曲塞500mg／m^2,第1天静脉滴注;顺铂：75mg／m^2,第1天静脉滴注,或顺铂30mg／m^2,静脉滴注,连用3d。每3周为1个周期重复,连用2～6个周期,进行疗效评价。结果可评价32例病例中,无CR,PR11例,SDl4例,PD7例。有效率为34．38％,疾病控制率为78．13％;临床受益反应率为71．88％。全组毒副反应较轻,主要为骨髓抑制及胃肠道反应,无治疗相关死亡。结论培美曲塞联合顺铂一线治疗晚期非小细胞肺癌疗效肯定,毒副反应可以耐受,可推荐作为晚期非小细胞肺癌的规范一线治疗方法。     

吉非替尼一线治疗老年晚期非小细胞肺癌疗效观察

目的：评价吉非替尼治疗非小细胞肺癌的疗效和毒副作用。方法：52例非小细胞肺癌患者,均未接受过一线治疗。治疗方案为吉非替尼250mg,qd,单药口服,每月1次胸腹部CT评价疗效。结果：52例患者中2例达完全缓解（CR）,11例部分缓解（PR）,20例稳定（SD）,全组有效率（CR＋PR）为25.0%,疾病控制率（CR＋PR＋SD）为63.5%。腺癌组有效率为31.3%,疾病控制率为71.9%;非腺癌组有效率为15.0%,疾病控制率为50.0%,二者之间差异有统计学意义（P〈0.05）。常见的毒副作用为皮疹和腹泻,Ⅰ、Ⅱ度不良反应皮疹（42.3%）和腹泻（26.9%）未见间质性肺病和常见的血液学毒性出现。结论：吉非替尼对于老年晚期非小细胞肺癌有较好的有效性和安全性。     

培美曲塞治疗晚期复发非小细胞肺癌临床观察

目的评价培美曲塞治疗晚期化疗后进展的非小细胞肺癌的疗效和毒副反应。方法46例经病理确诊既往化疗失败的晚期非小细胞肺癌患者,培美曲塞500mg／m^2静脉滴注,第1天,每21d为1个周期,并口服地塞米松、叶酸和肌内注射维生素B12以减轻毒副反应。根据RECIST标准对客观缓解率进行评价,毒副反应评价按美国NCI制定的毒性评价标准。结果46例可评价,总RR为10．6％。疾病控制率为45．7％,中位无进展生存期为3个月,中位生存期为7个月。毒副反应主要是中性粒细胞下降。结论培美曲塞治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性。     

吉非替尼治疗局部晚期和转移性非小细胞肺癌疗效相关性分析

目的:分析吉非替尼治疗局部晚期或转移性非小细胞肺癌(NSCLC)的疗效、中位生存期、无进展生存期及对症状的控制,同时分析与疗效和生存期可能相关的因素。方法:46例局部晚期或转移性NSCLC口服吉非替尼250 mg.d-1,直至出现肿瘤进展或不可耐受的毒副反应。服药前及服药后每4周进行肿瘤和全身评估。结果:46例可评价病例中,无完全缓解(CR),部分缓解(PR)14例,病情稳定(SD)20例,疾病进展(PD)12例。全组缓解率ORR为30.4%,疾病控制率DCR为73.9%。疾病相关症状缓解率为71.7%,中位症状缓解时间为8 d。症状改善持续中位时间为6.2个月;中位疾病进展时间6个月。中位生存期10.2个月,女性、腺癌、肺内病灶小或肺内弥漫病灶、有皮疹和腹泻的患者疾病控制率高,近期疗效好。主要不良反应为皮疹、腹泻。结论:吉非替尼治疗局部晚期和转移性非小细胞肺癌有较好近期疗效和生存益处。     

紫杉醇联合顺铂双周和周疗法治疗晚期非小细胞肺癌的疗效比较

目的:比较和评价紫杉醇联合顺铂双周和周疗法治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒副反应.方法:经病理和细胞学证实的60例Ⅲ、Ⅳ期NSCLC患者随机分为两组.双周疗法组30例:紫杉醇 80 mg/m2 ,顺铂 40 mg/m2, iv gtt d1、d8,第21天重复;周疗法组30例:紫杉醇 40 mg/m2,顺铂 30 mg/m2 iv gtt d1、d8、d15,第28天重复.测定给药后 3 h、12 h、24 h 的血药浓度,并评价经化疗2周期后的疗效和毒副反应.结果:双周疗法和周疗法的有效率分别为40.0%和36.7%,无统计学上的差异,但双周疗法的毒副反应发生率较低.结论:紫杉醇联合顺铂双周方案治疗晚期NSCLC较周疗法更为经济安全有效.拟增加病例数做进一步深入研究.     

Erlotinib and pemetrexed as maintenance therapy for advanced non-small-cell lung cancer: a systematic review and indirect comparison

Abstract

Background:

Two new agents have recently been licensed as maintenance therapy for advanced non-small-cell lung cancer (NSCLC) by the US Food and Drug Administration. This paper aims to systematically review the evidence from all available clinical trials of erlotinib and pemetrexed as maintenance therapy for advanced NSCLC.     

Prognostic performance of proteomic testing in advanced non-small cell lung cancer: a systematic literature review and meta-analysis

Abstract

Objective

Timely assessment of patient-specific prognosis is critical to oncology care involving a shared decision-making approach, but clinical prognostic factors traditionally used in NSCLC have limitations. We examine a proteomic test to address these limitations.     

吉非替尼与重组人血管内皮抑制素注射液联合治疗非小细胞肺癌的临床疗效及安全性观察

目的 探讨吉非替尼与重组人血管内皮抑制素注射液联合治疗非小细胞肺癌的临床疗效及安全性。方法 以河南省直第三人民医院2012年1月—2014年1月58例非小细胞肺癌化疗患者为研究对象,根据入院单双号将入选者随机分为对照组和研究组,每组29例,对照组患者单用吉非替尼治疗,研究组患者在此基础上联合重组人血管内皮抑制素注射液治疗,21 d为1个疗程,共进行4个疗程。比较两组患者的临床疗效、各肿瘤标志物水平变化、不良反应发生率及预后情况。结果 研究组及对照组患者客观缓解率（ORR）分别为86.21%、55.17%,两组比较存在显著性差异（P<0.05）。治疗前两组患者各肿瘤标志物水平比较无显著性差异,治疗后两组患者各肿瘤标志物水平均显著降低,前后比较存在显著性差异（P<0.05）;治疗后研究组患者各肿瘤标志物水平降低程度显著优于对照组,两组比较存在显著性差异（P<0.05）。随访3年后,研究组患者的生存率、中位生存期及中位无进展生存期均显著高于对照组,两组比较存在显著差异性（P<0.05）,两组不良反应的发生率比较无显著性差异。结论 吉非替尼与重组人血管内皮抑制素注射液联合应用可有效提高临床疗效,延长生存期,降低各肿瘤标志物水平,且不增加不良反应,安全性较高,值得在非小细胞肺癌的治疗中进行推广。