分子靶向药物治疗晚期胃肠道间质瘤的安全性及有效性分析

目的 系统评价分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼对比安慰剂或最佳支持治疗治疗晚期或转移性胃肠道间质瘤（gastrointestinal stromal tumour,GIST）的有效性与安全性。方法 计算机检索Pubmed、Embase、Cochrane Library、中国知网、万方数据库和维普等数据库,按照文献纳入标准和排除标准选择应用分子靶向药物治疗GIST的临床研究,RevMan 5.3软件进行meta分析。其中,试验组为近年来相继上市的酪氨酸激酶抑制剂分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼,对照组为安慰剂或最佳支持治疗。观察终点包括无进展生存期（progression-free survival,PFS）、总生存期（overall survival,OS）和3~4级不良反应发生率。结果 共纳入7项临床研究,总样本量为1 528例。Meta分析结果显示,分子靶向药物与对照组相比,PFS时间（HR=0.34,95%CI：0.26~0.44,P<0.001）,OS时间（HR=0.38,95%CI：0.17~0.85,P<0.02）均明显延长。在不良反应方面,分子靶向药物组可使3~4级不良反应（RR=4.47,95%CI：2.12~9.39,P<0.000 1）的发生率明显增高,主要是中性粒细胞减少、高血压、手足综合征、皮疹、腹泻和疲劳。结论 分子靶向药物治疗晚期或转移性GIST可以延长患者的PFS和OS。虽然其不良反应发生率高于对照组,但患者仍可耐受。     

放疗在美罗华时代对局限期原发韦氏环弥漫大B细胞淋巴瘤的治疗价值

目的 分析在美罗华联合化疗背景下,放疗对局限期韦氏环弥漫大B细胞淋巴瘤的治疗价值。方法 收集2010年—2017年收治的93例Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤患者的临床资料,将仅接受美罗华联合CHOP或CHOP类似方案化疗的38例患者分为单纯化疗组,将接受化疗+巩固放疗的55例患者分为综合治疗组。采用Kaplan-Meier法计算无进展生存（PFS）、总生存（OS）、局部区域控制率（LRC）,并行单因素分析;采用Log-rank法检验两组患者生存差异,并行Cox多因素回归分析。结果 本研究患者随访中位时间47个月,3年存活病例67例。单纯化疗组和综合治疗组患者的3年PFS分别为76.1%和94.2%（P=0.036）,3年OS分别为78.6%和96.0%（P=0.032）,3年LRC分别为83.1%和98.1%（P=0.015）。其中62例化疗后疗效评估为完全缓解（CR）的患者中,单纯化疗组和综合治疗组的3年PFS、OS和LRC分别为87.8%和97.6%（P=0.164）、93.8%和97.4%（P=0.522）、87.8%和100.0%（P=0.028）。进一步单因素分析结果显示,年龄>60岁和化疗疗效未达CR是PFS和OS的不良预后因素,B症状和化疗疗效未达CR是LRC的不良预后因素。多因素分析结果显示,年龄>60岁、B症状、化疗疗效未达CR是患者PFS的不良预后因素,年龄>60岁、化疗疗效未达CR是OS的不良预后因素,B症状、化疗疗效未达CR和未放疗是LRC的不良预后因素。结论 Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤采用美罗华联合CHOP为主的化疗后的巩固性放疗可显著改善患者的PFS、OS和LRC,但仍需大样本和前瞻性研究进一步证实。     

脂质体多柔比星治疗恶性肿瘤临床疗效及安全性的系统评价

目的 评价脂质体多柔比星（脂质体阿霉素）治疗恶性肿瘤的临床疗效及安全性。方法 计算机检索中国学术文献总库（CNKI）、万方数字化期刊库、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）,PubMed数据库、Embase数据库和Cochrane Library数据库,脂质体多柔比星治疗恶性肿瘤的中英文随机对照试验,检索年限从建库至2017年1月。采用RevMan 5.3软件对各效应指标进行Meta分析。结果 纳入23篇RCT文献,计5 546名恶性肿瘤患者。Meta分析结果显示：治疗前后临床疗效I²=63%、OR=1.14[1.02,1.27],P=0.002;两组化疗后心脏毒性不良事件I²=0%,OR=0.18[0.10,0.33],P<0.000 01;脱发不良事件I²=77%,OR=0.24[0.17,0.35],P<0.000 01;神经毒性不良事件I²=46%,OR=0.65[0.42,0.99],P=0.05。结论 脂质体多柔比星治疗恶性肿瘤的临床疗效优于其他化疗方案,且毒副作用低,尤其在改善心脏毒性、脱发等不良事件方面明显优于其他化疗方案。     

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。     

阿帕替尼联合化疗在铂类敏感复发性卵巢癌患者中的疗效及安全性评价

目的 观察阿帕替尼联合多柔比星脂质体和顺铂方案化疗在铂类敏感复发性卵巢癌患者中的疗效以及药物不良反应。方法 选取我院2017年1月—2019年6月收治的84例铂类敏感复发性卵巢癌患者，采用随机数字分组法分为对照组和观察组，每组42例。对照组给予贝伐珠单抗联合多柔比星脂质体和顺铂化疗，观察组给予阿帕替尼联合多柔比星脂质体和顺铂化疗。主要研究终点：客观有效率（ORR）、疾病控制率（DCR）、中位总生存期（mOS）和中位无进展生存期（mPFS）；次要研究终点：腹水定量，血清人附睾蛋白4（HE4）、糖类抗原125（CA125）、血管内皮生长因子（VEGF）水平的变化，以及药物不良反应发生率。结果 治疗后，观察组患者实体瘤ORR、DCR分别为50.00%、78.57%，高于对照组的26.19%、57.14%（χ²=5.048， P=0.025； χ²=4.421， P=0.036）。观察组患者腹水总缓解率为71.43%，高于对照组的50.00%（χ²=4.043， P=0.044）。观察组患者血清HE4、CA125和VEGF水平低于对照组（t=8.136， P=0.019；t =7.351， P=0.024；t =9.311， P=0.014）。两组患者胃肠道反应、骨髓抑制和肝肾功能损伤发生率相比较，差异无统计学意义（χ²=0.207， P=0.649； χ²=0.762， P=0.383； χ²=0.454， P=0.500）。观察组患者手足综合征、高血压和口腔黏膜炎发生率高于对照组（χ²=4.141， P=0.042； χ²=6.891， P=0.009； χ²=6.574， P=0.010）。观察组患者mOS为17.5个月， mPFS为15.0个月，分别高于对照组患者的14.2个月和10.1个月（χ²=8.623， P=0.012； χ²=9.758， P=0.009）。结论 阿帕替尼联合多柔比星脂质体和顺铂方案化疗，在铂类敏感复发性卵巢癌患者中的疗效肯定，可延长其生存期，且不良反应可耐受，值得临床推广。     

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。     

脑心通胶囊联合他汀类药物治疗高脂血症的系统评价

目的 系统评价脑心通胶囊联合他汀类药物治疗高脂血症的疗效和安全性。方法 计算机检索Cochrane图书馆、PubMed、Embase、Medline、CNKI、CBM、VIP、万方等数据库,纳入相关随机对照研究（RCT）,并进行评价,采用Revman 5.3软件分析数据。结果 纳入14篇RCTs,共1 244例受试者。相比单独使用他汀类药物,脑心通联合他汀类药物的血脂总疗效提高[RR=1.20,95% CI（1.10,1.31）,P<0.000 1]。治疗后总胆固醇水平低于对照组[WMD=-0.79,95% CI（-1.06,-0.53）,P<0.000 01],其中联合阿托伐他汀钙亚组异质性较低（P=0.09,I²=48%）。治疗后甘油三酯水平低于对照组[WMD=-0.68,95% CI（-0.92,-0.45）,P<0.000 01]。治疗后高密度脂蛋白高于对照组[WMD=0.28,95% CI（0.18,0.37）,P=0<0.000 01]。治疗后低密度脂蛋白水平低于对照组[WMD=-0.53,95% CI（-0.87,-0.18）,P=0.003]。各组不良反应发生率差异均无统计学意义[RR=2.25,95% CI（0.71,7.16）,P=0.17]。结论 脑心通联合他汀类药物治疗高脂血症疗效明显,对TC、TG、HDL-C、LDL-C的改善有效,联合阿托伐他汀钙对TC改善的疗效较为确切,不良反应发生率未见与其他药物有明显差异,推荐临床联合应用,并建议补充更多高质量的相关研究。     

慢性鼻-鼻窦炎伴鼻息肉术后复发的预测模型建立

目的 研究慢性鼻-鼻窦炎伴鼻息肉术后复发的预测模型建立。方法 选择2014年9月至2018年6月在南京大学医学院附属鼓楼医院高淳分院治疗的258例鼻-鼻窦炎伴鼻息肉患者作为模型建立组,建立术后复发的预测模型,选择同期本院收治的134例患者验证模型的区分度和校准度。结果 logistic回归分析结果显示,吸烟史（OR=2.998,95% CI：2.095~4.292）、鼻窦总积分（OR=1.489,95% CI：1.129~1.963）、支气管哮喘（OR=2.186,95% CI：1.688~2.831）、变应性鼻炎（OR=1.740,95% CI：1.403~2.159）、头/面疼痛评分（OR=2.083,95% CI：1.637~2.651）及嗅觉损伤评分（OR=1.879,95% CI：1.509~2.341）是患者术后复发的影响因素（P<0.05）。结论 吸烟史、鼻窦总积分、支气管哮喘、变应性鼻炎、头/面疼痛评分及嗅觉损伤评分等影响因素建立预测模型可有效预测患者术后复发。     

康艾注射液对晚期大肠癌化疗患者有效性及不良反应的Meta分析

目的 系统分析康艾注射液治疗晚期大肠癌临床疗效及不良反应发生情况。方法 检索中国学术期刊全文数据库（CNKI）、万方数据库、中国生物医学文献数据库（CBM）、维普生物医学数据库（VIP）、Cochrane Library、PubMed、Embase等中英文数据库中关于康艾注射液治疗晚期大肠癌化疗患者的临床随机对照试验（RCT），检索时限均为建库至2023年4月，采用RevMan 5.3软件进行Meta分析。结果 共纳入20项RCTs，Meta分析结果显示：与对照组比较，康艾注射液治疗组可提高患者临床总缓解率［RR＝1.34，95% CI（1.23，1.45），P<0.01］，降低肝损伤发生率［RR＝0.38，95% CI（0.29，0.49），P<0.01］、肾损伤发生率［RR＝0.43，95% CI（0.24，0.78），P=0.08］；白细胞下降发生率［RR＝0.67，95% CI（0.57，0.79），P<0.01］、血小板下降发生率［RR＝0.73，95% CI（0.53，1.00），P=0.05］、恶心呕吐发生率［RR＝0.46，95% CI（0.37，0.57），P<0.01］、腹泻发生率［RR＝0.55，95% CI（0.36，0.85），P=0.007］、神经毒性发生率［RR＝0.54，95% CI（0.38，0.77），P=0.000 6］、卡氏功能状态（KPS）评分上升率［RR＝1.56，95% CI（1.30，1.87），P<0.01］。结论 康艾注射液对肠癌晚期化疗患者可以起到增效减毒的作用，可以有效降低化疗所致的不良反应，降低肝肾损伤及其他不良反应的发生率，提升治疗效果，提高患者生存质量，但不能有效提升血小板水平，未来仍需进一步评估。     

艾司氯胺酮鼻腔喷雾剂辅助治疗难治性抑郁症安全性meta分析

目的 采用meta分析全面了解艾司氯胺酮鼻腔喷雾剂辅助治疗难治性抑郁症的安全性。方法 搜索艾司氯胺酮鼻腔喷雾剂+口服抗抑郁药的随机对照试验，并进行meta分析。结果 最终5个随机对照试验，1 019例患者纳入研究。与对照组比较，试验组出现了更多的解离症状（RR=6.35，95% CI，2.84~14.23，P<0.000 01）、镇静（RR=5.47，95% CI，2.05~14.57，P=0.000 7）、嗜睡（RR=2.66，95% CI，1.30~5.44，P=0.007）、头痛（RR=1.38，95% CI，1.05~1.83，P=0.02）、眩晕（RR=5.87，95% CI，3.30~69.79，P<0.000 01）、头晕（RR=2.98，95% CI，1.33~6.68，P=0.008）、感觉迟钝（RR=10.25，95% CI，3.65~28.83，P<0.000 1）、焦虑（RR=2.01，95% CI，1.20~3.37，P=0.008）、感觉异常（RR=6.62，95% CI，2.75~15.98，P<0.000 1）、恶心（RR=4.05，95% CI，2.71~6.05，P<0.000 01）、味觉异常（RR=1.81，95% CI，1.35~2.42，P<0.000 1）。亚组分析显示，与对照组比较，艾司氯胺酮鼻腔喷雾剂28 mg组不良反应没有统计学意义；除了嗜睡、头痛、味觉异常以外，56，84 mg 2个亚组的不良反应有统计学意义。结论 艾司氯胺酮鼻腔喷雾剂辅助治疗会增加患者不良反应，但是不良反应轻微。     

Efficacy and safety of doublet versus single agent as salvage treatment for metastatic breast cancer pretreated with anthracyclines and taxanes: a systematic review and meta-analysis

Aim: To perform a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of doublet versus single agent as salvage treatment for pretreated metastatic breast cancer.

Methods: A comprehensive literature search was performed to identify relevant randomized controlled trials (RCTs). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0).

Results: Thirteen RCTs involving 4878 pretreated metastatic breast cancer patients were ultimately identified. The pooled results demonstrated that doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01–1.27, p?<?.001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73–0.96, p?=?.011), but not OS (HR 0.93, 95% CI: 0.86–1.01, p?=?.065). Similar results were observed in sub-group analysis according to treatment regimens. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were observed in doublet combination therapy.

Conclusions: In comparison with a single agent alone, doublet combination therapy as salvage treatment for pretreated metastatic breast cancer patients significantly improves ORR and PFS, but not OS. Further studies are recommended to identify patients who will most likely benefit from the appropriate doublet combination therapy.     

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.     

Cabozantinib for the treatment of renal cell carcinoma

Introduction: Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy.

Areas covered:The preclinical development and scientific rationale, pharmacokinetics, and clinical efficacy and safety of cabozantinib for the treatment of advanced RCC are reviewed. The use of cabozantinib in clinical practice with the growing number of available treatments for advanced RCC is discussed.

Expert opinion: Cabozantinib is the only therapy for advanced RCC that has improved PFS, ORR, and OS in a pivotal phase 3 trial after prior antiangiogenic therapy. While no clinical trials have been published comparing cabozantinib with another TKI, available clinical data suggest it could be the most efficacious TKI for second-line therapy. Preliminary encouraging results have also been reported in a phase 2 trial in untreated poor- and intermediate- risk patients with RCC, indicating that treatment with cabozantinib may also be beneficial in the first-line setting.     

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.     

Amrubicin for non-small-cell lung cancer and small-cell lung cancer

Summary Amrubicin is a totally synthetic anthracycline anticancer drug and a potent topoisomerase II inhibitor. Recently, amrubicin was approved in Japan for the treatment of small- and non-small-cell lung cancers (SCLC and NSCLC). Here, we review the efficacy and toxicities of amrubicin monotherapy and amrubicin in combination with cisplatin for extensive-disease SCLC (ED-SCLC), and of amrubicin monotherapy for advanced NSCLC, as observed in the clinical trials. Recommended dosage for previously untreated advanced NCSLC was 45 mg/m²/day by intravenous administration for 3 days. Dose-limiting toxicities were leucopenia, thrombocytopenia, and gastrointestinal disturbance. Response rate was 27.9% for advanced NSCLC, and 75.8% for ED-SCLC with a median survival time (MST) of 11.7 months. Recommended dosage of amrubicin was 40 mg/m²/day in combination with cisplatin at 60 mg/m²/day, with MST of 13.6 months and 1-year survival rate of 56.1%. In sensitive or refractory relapsed SCLC, response rate was 52 and 50%, progression-free survival was 4.2 and 2.6 months, overall survival was 11.6 and 10.3 months, and 1-year survival rate was 46 and 40%, respectively. These results are promising for the treatment of both NSCLC and SCLC. Further clinical trials will clarify the status of amrubicin in the treatment of lung cancer.     

Predictive effect of PD-L1 expression for immune checkpoint inhibitor (PD-1/PD-L1 inhibitors) treatment for non-small cell lung cancer: A meta-analysis

BackgroundProgrammed death-ligand-1 (PD-L1) is a well-known predictive biomarker in non-small cell lung cancer (NSCLC) patients, however, its accuracy remains controversial. Here, we investigated the correlation between PD-L1 expression level and efficacy of its inhibitors, and hence assessed the predictive effect of PD-L1 expression.MethodsStudies that evaluated the efficacy of programmed death-1 (PD-1)/ PD-L1 inhibitors in advanced NSCLC patients according to tumor PD-L1 expression levels were searched for on Medline, Cochrane Library, and Embase. The pooled risk ratio (RR) and 95% confidence intervals (95% CIs) were calculated for the objective response rate (ORR) with overall survival (OS) and progression-free survival (PFS) were measured in terms of hazard ratio (HR) and the corresponding 95% CIs.Results1432 NSCLC patients from six randomized controlled trials (RCTs) were included and three PD-1/PD-L1 inhibitors (atezolizumab, nivolumab, and pembrolizumab) were used to treat the patients. A significantly higher ORR was observed in the high PD-L1 expression group compared to the low expression group (0.35 [95% CI, 0.30–0.40] vs 0.11 [95% CI, 0.09–0.14]). The results of the subgroup analysis, grouped by the type of drugs and antibodies which assess immune checkpoint inhibitors were identical with the pooled result. However, our study showed that PD-L1 expression was neither prognostic nor predictive of overall survival (OS) or progression-free survival (PFS) in patients treated with PD-1/PD-L1 inhibitors compared to chemotherapy.ConclusionsPD-L1 can be a predictive biomarker for ORR. Nevertheless, PD-L1 expression is not a good predictive tool for OS and PFS.     

Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: a retrospective,single-institution study

Background Prior to the 2008 advent of sorafenib, traditional cytotoxic agents were the therapeutic mainstay for patients with advanced hepatocellular carcinoma (HCC). We thus undertook a clinical study of sorafinib and conventional cytotoxic therapy for HCC, comparing efficacy and safety. Methods From January, 2002 to December, 2009, 173 patients with unresectable HCC were reviewed retrospectively. Among them, 44 (25.4%) had been treated with sorafenib, and the remainder had received cytotoxic therapy (CTX). We evaluated objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicity profiles. Results Median OS of sorafinib was 23.0 weeks (95% CI, 8.1–37.9) vs 43.6 weeks (95% CI, 34.0–53.2) for CTX. Likewise, median PFS was 11.1 weeks (95% CI, 6.5–15.8) vs 12.4 weeks (95% CI, 8.1–16.7) for sorafenib and CTX, respectively. Neither parameter differed significantly (OS, p = 0.105; PFS, p = 0.496). ORR and disease control rate for sorafenib were 2.3% and 52.3% vs 6.2% and 43.4% for CTX. CTX-treated patients experienced more Grade 3/4 neutropenia (19.7% vs 0% for sorafenib), while sorafenib therapy was more often linked to dermatologic toxicities (all grades), such as hand-foot skin reaction, rash, and pruritus. Conclusion Although sorafenib has become the treatment of choice for advanced HCC, there are still unsettled issues regarding the optimal use of sorafenib. Our analysis indicates that conventional CTX can be another option of treatment for advanced HCC. To improve clinical outcomes, further prospective investigations which define the role of CTX are needed.     

Multitargeted antiangiogenic tyrosine kinase inhibitors combined to chemotherapy in metastatic breast cancer: a systematic review and meta-analysis

Purpose

We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer.

Methods

PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived.

Results

Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70–1.04, P?=?0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89–1.18, P?=?0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30–1.91, P?=?0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55–0.82, P?=?0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs.

Conclusion

Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding.