尼洛替尼与伊马替尼治疗慢性粒细胞白血病早期临床疗效比较

目的 比较尼洛替尼与伊马替尼治疗慢性粒细胞白血病（CML）的早期（3个月时）疗效以及安全性。方法 选取2007年1月至2017年12月安徽省立医院确诊CML的患者129例,采用随机数字表法按照1∶7分为尼洛替尼组（18例）和伊马替尼组（111例）。两组患者服药3个月后门诊复查骨髓形态学、BCR-ABL融合基因国际标准值（BCR-ABL^IS）,比较两组患者的BCR-ABL^IS结果,评价两组患者的疗效（主要指标为BCR-ABL^IS≤10%的达标率、BCR-ABL^IS≤0.0032%的比例）以及药物的安全性（白细胞减少、血小板减少、贫血等血液学毒性;Q-T间期延长,以及肝功能损害、骨骼肌肉疼痛、水肿、皮疹、消化道症状等不良反应发生情况）。结果 尼洛替尼组患者治疗3个月时达到BCR-ABL^IS≤10%、BCR-ABL^IS≤0.0032%的比例均高于伊马替尼组（94.44%vs 69.37%;55.55%vs 27.92%）,差异均有统计学意义（P<0.05）;两组患者药物安全性比较,差异无统计学意义（P>0.05）。结论 尼洛替尼治疗CML的早期分子学反应达标率以及患者分子学反应的深度均高于伊马替尼组,两种药物不良反应发生情况无显著差异。     

尼洛替尼和伊马替尼治疗初诊CML-CP患者的疗效及不良反应比较

目的 比较尼洛替尼和伊马替尼治疗慢性髓系白血病慢性期（CML-CP）的疗效及不良反应。方法 选择2017年1～10月安徽医科大学第一附属医院门诊随访的初诊为CML-CP且初诊时即服用尼洛替尼超过12个月的患者30例为观察组,同时收集30例初诊为CML-CP且初诊时即服用伊马替尼超过12个月的患者为对照组。观察组予尼洛替尼300~400 mg,12小时口服1次,对照组予伊马替尼400 mg,每天口服1次。所有患者服药后3、6、12个月进行BCR-ABL^IS转录水平、Ph染色体转录水平及不良反应的检测。比较两组患者服药后早期分子生物学反应获得率（3、6个月）,主要分子生物学反应（MMR）获得率（3、6、12个月）,完全细胞遗传学缓解（CCyR,Ph=0）获得率（3、6、12个月）及不良反应。结果 在早期分子生物学反应（3、6个月）获得率（80.0%比53.3%,86.7%比63.3%）尼洛替尼组高于伊马替尼组（P<0.05）;3、6、12个月的MMR获得率分别为16.7%比6.7%、46.7%比20.0%、60.0%比25.9%,尼洛替尼组高于伊马替尼组,6、12个月时的差异有统计学意义（P<0.05）。在细胞遗传学方面,两组患者3、6、12个月的CCyR获得率分别为83.3%比66.7%、90.0%比76.7%、92.0%比85.2%,差异均无统计学意义（P>0.05）。两组患者均有血液毒性反应,但Ⅲ~Ⅳ不良反应少见,大多具有自限性。非血液学方面毒副作用尼洛替尼组主要表现为生化指标的异常,伊马替尼组主要表现为水肿,Ⅲ~Ⅳ不良反应少见,多数可自行恢复。结论 尼洛替尼治疗初诊CML-CP疗效更佳,但其生化方面的毒副作用更突出。     

舒尼替尼对胃肠道间质瘤患者二线治疗的临床观察

目的 探讨二线药物舒尼替尼治疗胃肠道间质瘤(GIST)的疗效及安全性.方法 回顾性分析经病理组织和免疫组化确诊的GIST患者32例,所有的患者均用二线药物舒尼替尼治疗,37.5 mg·d-1口服,连续给药服用.观察评估舒尼替尼的不良反应及患者的生存时间.结果 舒尼替尼治疗GIST的不良反应轻微,且均可控制.32例患者接受舒尼替尼治疗的时间为3~72个月,中位治疗时间为24个月.获得完全缓解(CR)1例,部分缓解(PR)7例,稳定期(SD)16例,进展(PD)8例,有效率25.0%,疾病控制率75.0%.32例患者中,中位随访时间为96周,中位无进展生存期(PFS)为55周,中位总生存时间(OS)为96周.结论 舒尼替尼治疗伊马替尼耐药进展的GIST疗效可靠,不良反应轻微,安全可控.     

舒尼替尼联合多靶点抗原肽自体免疫细胞治疗晚期转移性肾细胞癌的临床疗效及安全性

目的 探究舒尼替尼联合多靶点抗原肽自体免疫细胞技术（MASCT）治疗晚期转移性肾细胞癌（RCC）的临床疗效及安全性。方法 选取本院2016年1月—2017年1月收治的52例晚期转移性RCC患者,根据治疗方案的不同分为对照组（22例,采用MASCT治疗）和观察组（30例,采用舒尼替尼联合MASCT治疗）。对比两组患者的临床疗效,采用酶联免疫吸附法（ELISA）检测患者治疗前后白介素-17（IL-17）、血管内皮生长因子（VEGF）、低氧诱导因子-1α（HIF-1α）和血小板衍化生长因子（PDGF）的血清水平,计算肿瘤微血管密度（MVD）,并对比两组患者的无进展生存期（PFS）、总生存期（OS）及不良反应发生率。结果 观察组临床治疗有效率为86.7%,显著高于对照组的59.1%（P<0.05）。治疗后,两组患者血清IL-17、VEGF、HIF-1α及PDGF水平均显著降低,且观察组显著低于对照组（P<0.05）。治疗后,两组患者MVD均显著降低,且观察组显著低于对照组（P<0.05）。观察组患者PFS和OS均显著长于对照组（P<0.05）。两组患者恶心、呕吐、腹泻、乏力、便秘、面部水肿、脱发、高血压、白发、血小板减少、中性粒细胞减少、贫血、尿酸升高、甲状腺功能降低、谷丙转氨酶升高、口腔黏膜炎、皮肤色素脱失、皮肤黄染、手足综合征等不良反应发生率比较,差异均无统计学意义（P>0.05）。结论 舒尼替尼联合MASCT治疗晚期转移性RCC可提高临床治疗效果,降低相关血清肿瘤标志物水平,延长生存期,且不增加不良反应,具有一定的临床应用价值。     

安罗替尼联合替吉奥二线治疗晚期食管癌的疗效及安全性

目的 探讨安罗替尼联合替吉奥二线治疗晚期食管癌的疗效及安全性。方法 选取2018年6月至2019年9月安徽医科大学附属巢湖医院收治的60例一线化疗后失败或缓解后再进展的晚期食管癌患者,采用随机数字表法分为观察组和对照组,各30例,观察组给予安罗替尼联合替吉奥方案,对照组给予单药替吉奥方案,每2周期进行疗效评价,分析两组有效率（ORR）、疾病控制率（DCR）、中位无进展生存时间（PFS）,同时比较两组乏力、高血压、胃肠道反应、手足皮肤反应、口腔粘膜炎、骨髓抑制、肝功能损害、蛋白尿等不良反应差异。结果 观察组ORR为23.3%（7/30）,对照组ORR为10.0%（3/30）,两组差异无统计学意义（P>0.05）。观察组DCR为76.7%（23/30）,PFS为5.6个月;对照组DCR为46.7%（14/30）,PFS为1.4个月,两组DCR、PFS差异均有统计学意义（P<0.05）。观察组高血压发生率高于对照组（P<0.05）,两组余不良反应发生率差异均无统计学意义（P>0.05）。所有不良反应经对症处理后均缓解。结论 安罗替尼联合替吉奥方案治疗晚期食管癌疗效及安全性尚可,不良反应可耐受,值得临床推广。     

安罗替尼治疗恶性肿瘤的不良反应分析

目的 了解安罗替尼（AL3818）的安全性,以便更好地应用该药,为患者提供更安全、有效的治疗。方法 收集安罗替尼在临床应用中的常见不良反应信息,结合现有的临床数据,对比安罗替尼与同类抗肿瘤药物的不良反应类型及发生率的差别。结果 安罗替尼的不良反应主要为食欲减退、乏力、蛋白尿、血尿、腹痛、呕吐、腹泻、高血压和手足综合征等,其中1级、2级不良反应78例（96.30%）,3级不良反应3例（3.70%）。与同类抗肿瘤药物相比,安罗替尼的出血、高血压、蛋白尿等不良反应发生率明显低于阿帕替尼和贝伐珠单抗,差异均具有统计学意义（P<0.05）。结论 盐酸安罗替尼胶囊用于治疗恶性肿瘤安全性较高。     

早期应用替罗非班对急性ST段抬高型心肌梗死患者PCI术后冠脉血流及并发症影响的Meta-分析

目的 系统评价早期应用替罗非班对急性ST段抬高型心肌梗死（STEMI）经皮冠状动脉介入（PCI）术后冠脉血流及并发症影响。方法 检索PubMed、Embase、Cochrane图书馆、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库关于STEMI患者急诊行PCI并早期应用替罗非班的临床对照研究（RCT）,检索年限均为建库起至2020年4月30日。试验组为PCI术前开始应用替罗非班,对照组为PCI术中或术后应用替罗非班,数据提取和质量评价,应用RevMan 5.3软件进行Meta-分析。结果 共纳入15项RCT,共计2 214例患者。Meta-分析结果显示,术前应用替罗非班组较术中或术后用药组,PCI术后TIMI血流分级为3级（RR=1.10,95%CI=1.06~1.15,P<0.01）和（RR=1.10,95%CI=1.03~1.17,P<0.01）、ST段下落幅度（SMD=0.44,95%CI=0.17~0.70,P=0.001）和（SMD=1.85,95%CI=1.53~2.17,P<0.01）、ST段回落率（RR=1.51,95%CI=1.20~1.89,P<0.01）和（RR=1.20,95%CI=1.05~1.39,P=0.01）均显著优于术中或术后用药;术前应用组提高左心室射血分数（LVEF%）（SMD=0.46,95%CI=0.13~0.79,P=0.007）和降低主要心血管不良事件（MACE）发生率（RR=0.53,95%CI=0.39~0.73,P<0.01）均优于术中用药组。术前应用组与术后应用组的LVEF%和MACE发生率比较均无显著性差异。术前应用组出血及并发症发生率与术中及术后应用组比较均无显著性差异。结论 与PCI术中及术后应用替罗非班相比,术前应用更能显著改善STEMI患者微循环障碍、增加心肌组织有效的再灌注、减少心肌梗死范围。     

替加环素联合舒巴坦制剂治疗鲍曼不动杆菌感染的meta分析

目的 系统评价替加环素联合舒巴坦制剂治疗多重耐药/泛耐药鲍曼不动杆菌感染的疗效。方法 系统检索CNKI、Wangfang Data、CBM、PubMed、The Cochrane Library、Web of science、Embase,检索时间为建库至2018年7月1日,检索方式为主题词结合自由词检索,语种不限,由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行meta分析。结果 检索到相关文献共1 062篇,按纳入及排除标准从中选择符合标准的46篇文献。Meta分析结果显示,替加环素联合舒巴坦制剂对比单用替加环素或单用舒巴坦制剂在总的有效率和细菌清除率方面有一定优势[OR=3.90,95%CI（3.25,4.68）,P<0.000 01],[OR=3.29,95%CI（2.76,3.92）,P<0.000 01];在不良反应方面,联合用药不会增加其发生率[OR=0.87,95%CI（0.67,1.14）,P=0.31]。亚组分析显示,联用舒巴坦制剂可降低替加环素的不良反应发生率[OR=0.51,95%CI（0.28,0.93）,P=0.03]。结论 替加环素联合舒巴坦制剂治疗多重耐药/泛耐药鲍曼不动杆菌感染优于单用替加环素或单用舒巴坦制剂。     

LC-MS/MS法测定大鼠血清中尼洛替尼浓度及其药动学研究

摘 要 目的:建立快速、灵敏的高效液相色谱串联质谱电喷雾法测定大鼠血清中尼洛替尼的浓度,并进行大鼠尼洛替尼胶囊的药动学研究。方法: 以XDB C₁₈色谱柱分离,采用电喷雾离子源（ESI源）;以维拉帕米为内标,血清样品经乙腈沉淀蛋白后,以甲醇（含0.1%甲酸）∶水（含0.1%甲酸）= 50∶50为流动相,流速为0.35 ml·min^-1。以多反应监测（MRM）方式进行正离子检测,监测离子对分别是m/z 530.2→289.1（尼洛替尼）和内标m/z 455.3→165（维拉帕米）。结果:血清中尼洛替尼的线性范围在5～2000 ng·ml^-1良好。尼洛替尼在大鼠体内的主要药动学参数AUC_0-24、C_max、t_max、t_1/2z、CLz/F分别为(10 055.37±1 405.49) ng·h·ml^-1、(1 273.56±329.49) ng·ml^-1、(6.17±3.37) h、(1.86±1.04) h、(2.01±0.27) L·h^-1·kg^-1。结论:本试验建立的分析方法专属性好,灵敏度高,准确快捷,适用于尼洛替尼大鼠血清生物样品的快速检测。     

中国人群予以不同剂量阿替普酶治疗急性缺血性脑卒中的Meta-分析

目的 系统评价中国人群分别予以标准剂量（0.9 mg/kg）和低剂量（0.6 mg/kg）阿替普酶治疗急性缺血性脑卒中的临床疗效和安全性,为临床提供循证医学证据。方法 计算机检索EMbase、PubMed、中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）和万方数据库,收集急性缺血性脑卒中患者分别采用标准剂量和低剂量阿替普酶静脉溶栓的随机对照研究（RCT）,检索时限均为建库—2018年3月,提取数据后采用RevMan 5.2软件进行Meta-分析。结果 共纳入16个RCTs,1 745例患者。Meta-分析结果显示：标准剂量组在总有效率（RR=0.95,95%CI=0.92~0.99,P=0.01）、降低NIHSS评分（SMD=0.27,95%CI=0.14~0.40,P<0.001）、提高预后良好率（RR=0.85,95%CI=0.78~0.92,P=0.000 2）和降低脑出血率（RR=0.59,95%CI=0.38~0.92,P=0.02）方面均优于低剂量组,差异均有统计学意义（P<0.05）,但是病死率（RR=1.23,95%CI=0.84~1.80,P=0.28）差异无统计学意义。结论 现有证据表明,标准剂量阿替普酶静脉溶栓具有更好的临床疗效,但可能增加溶栓后脑出血的风险,临床医务人员应予以重点关注。     

Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

塞来昔布联合化疗对转移性或术后复发性晚期胃癌的疗效及药物不良反应

目的 分析塞来昔布联合化疗治疗转移性或术后复发性胃癌的疗效和安全性。方法 收集2010年9月至2016年12月转移性或术后复发性胃癌患者,分为塞来昔布+化疗组和单纯化疗组,治疗6个周期。比较两组患者间临床资料、无进展生存期（PFS）、总生存期（OS）的差异,并进一步分析COX-2阳性亚组的生存情况,评价药物安全性。结果 共纳入患者176例,塞来昔布+化疗组89例,单纯化疗组87例。两组患者客观缓解率、疾病控制率比较,差异均无统计学意义（P>0.05）。两组患者中位OS（P=0.59）和中位PFS（P=0.734）比较,差异均无统计学意义。塞来昔布+化疗组COX-2阳性患者中位OS为14个月,单纯化疗组COX-2阳性患者为10个月,差异有统计学意义（P=0.010）;塞来昔布+化疗组COX-2阳性患者中位PFS为7.5个月,单纯化疗组COX-2阳性患者为5个月,差异有统计学意义（P<0.001）。两组患者的药物不良反应均以恶心最为常见,但差异无统计学意义。结论 塞来昔布联合化疗可延长COX-2阳性晚期胃癌患者的OS和PFS,且不增加药物不良反应。     

氨柔比星用于小细胞肺癌二线治疗的荟萃分析

目的 系统评价氨柔比星治疗小细胞肺癌（small-cell lung cancer, SCLC）的疗效及安全性。方法 检索PubMed、EMBASE、CNKI及The Cochrane Library等数据库,收集有关氨柔比星治疗SCLC的研究;主要结局指标包括总有效率（overall response rate,ORR）、无进展生存率（progression free survival, PFS）、总生存率（overall survival, OS）及不良事件。结果 共有6项研究纳入,荟萃分析（Meta分析）显示,氨柔比星应用于SCLC二线治疗时的总有效率显著高于对照组[RR 1.72,95% CI（1.39,2.14）,P=0.000],但总生存率[HR 0.93,95% CI（0.81,1.07）,P=0.405]和无进展生存率[HR 0.98,95% CI（0.83,1.17）,P=0.456]与对照组相比无明显差异。结论 氨柔比星治疗SCLC的总有效率高于对照组,且PFS和OS与对照组相比无显著性差异（P=0.405,P=0.456）,因此,氨柔比星可作为SCLC的二线治疗药物。     

Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials

Objectives:

To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.

Patients and methods:

The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.

Results:

The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR?=?0.61, 95% CI 0.48 to 0.79, P?<?0.001 for bevacizumab; HR?=?0.71, 95% CI 0.59 to 0.87, P?=?0.001 for VEGFRIs; and HR?=?0.67, 95% CI 0.62 to 0.72, P?<?0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR?=?0.90, 95% CI 0.80 to 1.01, P?=?0.079), VEGFRIs showed no improvement (HR?=?0.92, 95% CI 0.75 to 1.11, P?=?0.368), and trebananib demonstrated a significant prolongation (HR?=?0.81, 95% CI 0.67 to 0.99, P?=?0.036). Bevacizumab was associated with more class-specific adverse events (RR?=?4.05, 95% CI 1.99 to 8.27, P?<?0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR?=?2.60, 95% CI 0.84 to 8.00, P?=?0.097).

Conclusions:

Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.     

Predictive value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis

BackgroundHigh neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are associated with poor prognosis in cancer patients treated with Immune checkpoint inhibitors (ICIs). However, whether this relationship exists in non-small cell lung cancer (NSCLC) patients remains unclear. Thus, this meta-analysis was conducted to investigate the prognostic role of NLR and PLR in NSCLC treated with ICIs.MethodsEligible studies that evaluated the value of pre-treatment or post-treatment NLR/PLR in NSCLC patients received ICIs were obtained by searching PubMed, Web of Science, Cochrane Library, and EMBASE. The pooled hazard ratio (HR) and 95% confidence interval (CI) were used to assess the relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS). Subgroup analysis and publication bias were conducted to investigate heterogeneity.Results1845 NSCLC patients from 21 studies were included and three ICIs(nivolumab, pembrolizumab, and atezolizumab) were used. Overall, high NLR was associated with poor OS (HR: 2.50, 95% CI:1.79–3.51, P < 0.001) and PFS (HR: 1.77, 95% CI:1.51–2.01, P < 0.001). Subgroup analyses were consistent with the pooled results. Similarly, the pooled results for PLR showed that elevated PLR was related to inferior OS (HR: 1.93, 95% CI: 1.51–2.01, P < 0.001) and PFS (HR: 1.57, 95%CI: 1.30–1.90, P < 0.001). However, the subgroup analysis based on test time indicated that there was no significant correlation between post-treatment PLR and survival outcomes.ConclusionNLR and pre-treatment PLR could serve as prognostic biomarkers in NSCLC patients treated with ICIs. However, the value of post-treatment PLR needs further to be evaluated.     

健脾益气和胃中药治疗糖尿病胃轻瘫的系统评价

目的 系统评价健脾益气和胃中药治疗糖尿病胃轻瘫的临床疗效和安全性。方法 检索PubMed、MEDLINE、TheCochrane Library、Embase、CBM、CNKI、VIP及万方等数据库,纳入符合条件的临床随机对照试验。按照Cochrane系统评价标准对纳入文献进行质量评价,应用RevMan 5.3软件进行Meta分析。结果 共纳入28个研究,2 370例患者。Meta分析结果显示,健脾益气和胃中药治疗糖尿病胃轻瘫的总有效率[RR=1.29,95% CI （1.24~1.35）,P<0.000 01]、对腹胀[MD=-0.31,95% CI （-0.42,-0.21）,P<0.000 01]、纳差[MD=-0.45,95% CI （-0.72,-0.18）,P=0.001]、嗳气[MD=-0.32,95% CI （-0.53,-0.10）,P=0.004]等临床症状的改善均优于西药。中药治疗组不良反应[RD=-0.03,95% CI （-0.06,-0.00）,P=0.03]及复发率[RR=0.25,95% CI （0.14,0.43）,P<0.000 1]均少于西药组。结论 健脾益气和胃中药能够有效治疗糖尿病胃轻瘫,但仍需大规模、高质量的临床随机对照研究加以验证。     

Real-world use of osimertinib in non–small cell lung cancer: ASTRIS study Korean subgroup analysis

Abstract

Objective: ASTRIS is a large real-world, open-label, multinational clinical study of osimertinib in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) who have previously received a tyrosine kinase inhibitor (TKI). We report data from the Korean ASTRIS subgroup.

Methods: Adult patients with locally advanced or metastatic NSCLC with a confirmed T790M mutation, WHO performance status of 0–2 and prior EGFR-TKI therapy, received osimertinib 80?mg once daily. Efficacy outcomes were overall survival (OS), investigator-assessed response rate (RR) and progression-free survival (PFS), and time to treatment discontinuation (TTD).

Results: At data cut-off (20 October 2017), 466 Korean patients were enrolled. Baseline EGFR molecular testing was mainly performed on biopsied tissue (75.1%). Baseline mutations co-occurring with T790M included exon 19 deletions (60.7%) and L858R (32.8%). 1-year OS was 82.7% (OS data not matured at data cut-off). Overall, RR was 71.0%, median PFS was 12.4?months and median TTD was 15.0?months. In patients with/without CNS metastases, RR was 68.0% and 79.6%, respectively; median PFS, 10.8 and 11.0?months, respectively; and median TTD, 11.2 and 14.7?months, respectively. Overall, 31.1% of patients experienced ≥1 adverse event (AE), leading to dose modification (12.0%), discontinuation (5.2%) or death (2.8%). Serious AEs (24.9%) included pulmonary embolism (1.7%), pleural effusion (1.7%), and pneumonia (1.5%).

Conclusion: In this real-world subgroup analysis of Korean patients in the ASTRIS study, osimertinib demonstrated comparable clinical efficacy to that attained in the global ASTRIS study and other clinical trials, with no new safety concerns.     

Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review

Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies.

Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI.

Results Included patients (n?=?325 for everolimus and n?=?127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with?<6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup.

Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors.

Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.     

Impact of intraoperative MRI-guided resection on resection and survival in patient with gliomas: a meta-analysis

Objective: This study addressed the benefit of intraoperative magnetic resonance imaging (iMRI) compared with conventional neuronavigation-guided resection in patients with gliomas.

Research design and methods: The Medline, PubMed, Cochrane, and Google Scholar databases were searched up to 26 September 2015. Randomized controlled trials (RCTs), two-arm prospective studies, and retrospective studies in patients with glioblastoma/glioma who had received surgical treatment were included.

Main outcome measures: The primary outcome measures were the extent of tumor resection and tumor size reduction for using iMRI-guided or conventional neuronavigation-guided neurosurgery. Secondary outcomes included impact of surgery on 6 month progression-free survival (PFS), 12 month overall survival (OS) rates and surgical duration.

Results: We found that iMRI was associated with greater rate of gross total resection (rGTR) compared with conventional neuronavigation procedures (3.16, 95% confidence interval [CI] 2.07–4.83, P?P values ≥.065). Intraoperative MRI was associated with a higher rate of progression-free survival (PFS) compared with conventional neuronavigation (odds ratio, 1.84; 95% CI 1.15–2.95; P?=?.012), but the rate of overall survival (OS) between groups was similar (P?=?.799). Limitations of the study included the fact that data from non-RCTs was used, the small study population, and heterogeneity of outcomes across studies.

Conclusions: Our findings indicate that iMRI more frequently resulted in more complete resections leading to improved PFS in patients with malignant gliomas.     

The value of surrogate endpoints for predicting real-world survival across five cancer types

Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints – progression-free survival (PFS) and time to progression (TTP) – to predict real-world OS across five cancers.

Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan–Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991–2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R² from linear regressions.

Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P?=?0.026). Among all real-world patients using sample treatments (N?=?309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P?=?0.194). Results were qualitatively similar using median absolute prediction error and R² metrics.

Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.