PD-1/PD-L1抑制剂对比化疗一线治疗晚期非小细胞肺癌的Meta分析

 目的 系统评价PD-1/PD-L1抑制剂对比化疗一线治疗晚期非小细胞肺癌的疗效及安全性。方法 通过Web of science等国内外数据库，ASCO会议摘要及杂志筛选文献，进行Meta分析。结果 纳入7项RCT研究，4 101例患者，荟萃分析显示抑制剂联合化疗对比化疗可显著延长患者的PFS（HR=0.59, 95%CI: 0.50~0.70, P<0.00001）、OS（HR=0.65, 95%CI: 0.46~0.92, P=0.02）及ORR（RR=1.72, 95%CI: 1.13~2.62, P=0.01）。亚组分析显示，抑制剂联合化疗可显著延长PFS及OS，且PD-L1表达程度越高，疗效获益越显著。而单药抑制剂对比化疗在延长晚期NSCLC患者的PFS（HR=0.87, 95%CI: 0.57~1.31, P=0.50）、OS（HR=0.82, 95%CI: 0.65~1.03, P=0.09）及提高ORR（RR=1.12, 95%CI: 0.55~2.28, P=0.76）方面两组差异无统计学意义。与化疗相比，单药抑制剂一线治疗PD-L1高表达的晚期NSCLC患者可显著延长OS，但在延长PFS方面未见明显优势。与化疗组相比，抑制剂联合化疗组3~4级不良反应发生率无明显改善（HR=1.09，95%CI: 0.99~1.20, P=0.09），而单药PD-1/PD-L1抑制剂组3~4级不良反应发生率低（RR=0.43, 95%CI: 0.36~0.52, P<0.00001）。 结论 PD-1/PD-L1抑制剂联合化疗一线治疗晚期NSCLC患者疗效优于化疗方案；PD-L1高表达者单药PD-1/PD-L1抑制剂可作为一线治疗的优先选择，且具有良好的安全性。     

贝伐珠单抗联合化疗一线治疗转移性乳腺癌的Meta分析

目的:通过Meta分析,探讨贝伐珠单抗联合化疗一线治疗转移性乳腺癌(MBC)的有效性和安全性。方法:通过PubMed、Medline、EMBASE、Cochrane图书馆、ASCO论文集、中国期刊全文数据库、万方数据库等数据库检索国内外已发表和未发表的相关文献。由2位评价者分别按检索策略收集资料,按纳入标准入选,主要对无疾病进展生存期(PFS)、总生存期(OS)、客观缓解率(ORR)和3～4级不良反应事件的发生率进行Meta分析。结果:共纳入5个随机对照临床研究(RCT),联合使用贝伐珠单抗一线化疗组PFS(RR=1.50;95%CI:1.31～1.72,P<0.001),OS(RR=1.06;95%CI:1.02～1.11,P=0.005)和ORR(RR=1.37;95%CI:1.26～1.49,P<0.001)与单药化疗组相比差异有统计学意义,3～4级高血压(RR=7.74;95%CI:1.33～45.00,P<0.001)和蛋白尿(RR=4.59;95%CI:2.15～9.79,P<0.001)的发生率与单药化疗组相比差异有统计学意义,而出血和血栓事件的发生率差异无统计学意义。结论:联合使用贝伐珠单抗一线治疗能显著提高MBC患者PFS、OS和ORR,可能增加高血压和蛋白尿的发生率,但不显著增加出血和血栓事件的发生率。     

雷莫芦单抗治疗晚期非小细胞肺癌有效性及安全性的Meta分析

[摘要] 目的: Meta分析雷莫芦单抗（ramucirumab）治疗晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的有效性及安全性。方法: 计算机检索Cochrane 图书馆（2017 年第8 期）、Web of Science、Pubmed、EMbase、万方数据库、中国期刊全文数据库(CNKI)、中国生物医学文献数据库（CBM）、中国科技期刊数据库和ASCO、ESMO主要会议数据库,检索时限均从建库至2017 年9 月1 日。收集雷莫芦单抗治疗晚期NSCLC的临床随机对照试验, 由2 位评价员独立筛选文献、提取数据并评估纳入研究的质量后,采用RevMan5.3 软件进行的实验组与对照组雷莫芦单抗治疗后NSCLC患者的无进展生存期（PFS）、总生存期（OS）、客观反应率（ORR）及不良反应等Meta 分析。结果：最终纳入3 项RCT进行Meta 分析,共计1 545 例NSCLC患者,其中雷莫芦单抗组777例,对照组768 例。试验组NSCLC患者的PFS 和OS均优于对照组[HR=0.77, 95%CI(0.69~0.85), P<0.01; HR=0.88, 95%CI(0.78~0.99), P<0.05];但雷莫芦单抗组和对照组ORR比较差异无统计学意义[RR=1.33, 95%CI(0.68~2.61), P>0.05]。雷莫芦单抗联合多西他赛对比多西他赛单药二线治疗可延长晚期NSCLC患者的PFS 和OS [HR=0.77, 95%CI(0.69~0.86), P<0.01 ; HR=0.86, 95%CI(0.76, 0.98), P<0.05];雷莫芦单抗试验组最严重的不良反应为高血压[RR=3.33,95%CI(1.83~6.05), P<0.01], 而恶心、呕吐、腹泻、食欲减退、疲劳、蛋白尿、中性粒细胞减少、白细胞减少、血小板减少、出血事件等两组差异均无统计学意义（均P>0.05）。结论：雷莫芦单抗治疗可延长晚期NSCLC患者的PFS和OS,其最主要的不良反应为高血压。     

抗VEGF与抗EGFR靶向药物联合化疗一线治疗转移结直肠癌Meta分析

目的 NCCN指南推荐抗VEGF或抗EGFR作为伴RAS野生型的转移结直肠癌(metastatic colorectal canc-er,mCRC)一线治疗的标准方案,但抗VEGF与抗EGFR在转移结直肠癌预后的差异性罕见系统评价参考.本研究拟通过系统评价分析抗VEGF与抗EGFR靶向药物联合化疗对转移结直肠癌疗效的影响.方法 计算机检索Cochrane、Pubmed、Web of science、Embase、ASCO、ESMO、Clinical Trials和中国生物医学文献数据库等,同时追溯参考文献.收集抗VEGF联合化疗对比抗EGFR联合化疗治疗mCRC头对头的随机对照试验(Randomized controlled trial,RCT),根据Cochrane系统评价手册5.3质量评价标准,采用Stata 12.0和Revman 5.3进行Meta分析.结果 共纳入3篇临床随机对照试验,共2014例研究对象.Meta分析结果显示,一线给予抗EGFR或抗VEGF联合化疗的mCRC患者,无论KRAS野生型(HR=1.03,95%CI为0.93~1.13)或RAS野生型(HR=0.92,95%CI为0.71~1.18)的无进展生存期(pogression free survival,PFS)均差异无统计学意义,P<0.05.一线给予抗EGFR联合化疗方案的总生存期(overall survival,OS)KRAS野生型(HR=0.82,95%CI为0.72~0.93)和RAS野生型患者(HR=0.79,95%CI为0.67~0.93)均优于抗VEGF联合化疗,P<0.05.mCRC伴KRAS野生型患者,接受抗EGFR联合化疗客观缓解率(objective re-sponse rate,ORR)显著提高,RR=0.84,95%CI为0.76~0.94;这种优势对于所有的RAS野生型患者更加明显,RR=0.80,95%CI为0.68~0.93.无论使用抗EGFR或抗VEGF联合化疗,左半结直肠癌患者相比右半结肠癌患者有生存获益PFS(HR=0.64,95%CI为0.45~0.91)及OS(HR=0.53,95%CI为0.36~0.76).结论 mCRC伴KRAS或RAS野生型患者的一线治疗,抗EGFR单克隆抗体可能是替代抗VEGF治疗作为晚期mCRC的初始治疗的最佳治疗方案.而对于肿瘤的位置而言,无论接受何种靶向药物治疗,左半结肠肿瘤相比右半结肠肿瘤的患者都具有更好的生存优势.     

含伊立替康方案一线治疗晚期胃癌的Meta分析

目的:采用Meta分析的方法探讨含伊立替康方案一线治疗晚期胃癌患者的疗效及安全性。方法:利用计算机检索中国生物医学文献数据库、中国期刊全文数据库、维普数据库、Cochrane Library、Pub Med、Embase及SCI等数据库,收集含伊立替康方案一线治疗晚期胃癌的临床随机对照试验(randomized control trail,RCT),主要结局指标包括总有效率(overall response rate,ORR)、无进展生存时间(progression free survival,PFS)、总生存期(overall survival,OS)及治疗的相关不良反应;以相对危险度(relative risk,RR)和风险比(hazard ratios,HR)为效应量,各效应量以95%可信区间(coni dence interval,CI)表示,采用Stata 12.0统计软件进行Meta分析。结果:最终共8个RCT,1 910例晚期胃癌患者纳入研究。Meta分析结果显示,伊立替康组患者的PFS(HR=0.82,95%CI:0.69~0.98,P=0.03)和OS(HR=0.88,95%CI:0.80~0.97,P=0.007)均较非伊立替康组明显延长,ORR(RR=1.56,95%CI:1.18~2.06,P=0.002)获得明显的提高。在不良反应方面,主要增加了患者腹泻事件的发生率(RR=3.57,95%CI:1.97~6.46,P<0.001),而中性粒细胞减少、血小板数减少、贫血、恶心及口腔黏膜炎事件的发生率差异无统计学意义。结论:以伊立替康为基础的化疗方案一线治疗晚期胃癌患者可提高ORR并延长PFS及OS;在不良反应方面,该方案增加了患者腹泻事件的发生率。     

化疗联合PD-1/PD-L1抑制剂治疗三阴性乳腺癌有效性和安全性的Meta分析

目的:利用循证医学手段,通过Meta分析评估化疗联合PD-1/PD-L1 抑制剂与单纯化疗治疗三阴性乳腺癌的安全性和有效性,从而为临床诊疗提供指导意见。方法:检索Pubmed、Embase、Cochrane图书馆、知网、万方、维普和CBM数据库从建库到2021年08月以来有关化疗联合PD-1/PD-L1 抑制剂治疗三阴性乳腺癌的文献。由两位研究者独立完成筛选文献、提取资料以及评估偏倚风险后,采用RevMan 5.3和STATA 15.1软件进行统计分析。结果:本次研究共纳入8篇文献。汇总结果表明联合治疗组患者的总生存期（overall survival,OS）和无进展生存期（progression-free survival,PFS）明显长于仅接受化疗的患者（HR=0.85,95%CI:0.75~0.96;HR=0.84,95%CI:0.73~0.97）。结果还表明联合治疗组患者的(complete remission rate,CRR)也显著高于仅接受化疗治疗的患者（RR=1.44,95%CI:1.10~1.89）。此外,联合治疗组的不良反应发生率高于单纯化疗组（RR=1.08,95%CI:1.03~1.14）。亚组分析的结果显示接受Atezolizumab联合化疗的患者的 OS 明显长于单独接受化疗的患者（HR=0.85,95%CI:0.75~0.96）,接受Atezolizumab或Pembrolizumab与化疗的联合治疗显著延长了患者的PFS（HR=0.80,95%CI:0.73~0.89;HR=0.79,95%CI:0.67~0.92）,然而接受Durvalumab联合化疗的患者OS和PFS较单纯化疗并无显著差异。结论:化疗联合 PD-1/PD-L1 抑制剂治疗三阴性乳腺癌比单独化疗更有效,但联合治疗有着更高的不良反应发生率。此外,Durvalumab与化疗药的联合使用并不能增加患者的OS和PFS。     

紫杉醇剂量密集化疗在原发性上皮性卵巢癌中疗效与安全性Meta分析

目的：系统评价紫杉醇剂量密集化疗在原发性上皮性卵巢癌中疗效与安全性。方法：检索Cochrane Library、Pubmed、Embase、Medline、中国知网（CNKI）、维普（VIP）、万方、中国生物医学文献数据库（CBM）等数据库并手工检索会议摘要及相关参考文献，应用Cochrane偏倚风险评估工具5.1版进行偏倚风险评价，RevMan 5.3行Meta分析。结果：纳入11项RCT研究共4590例患者，Meta分析结果显示紫杉醇剂量密集化疗与三周化疗方案无进展生存期（PFS）（HR=0.89，95%CI 0.77-1.04，P=0.21）、整体生存率（OS）（HR=0.94，95%CI 0.82-1.07，P=0.35）差异无统计学意义，同样未提升患者生存率、客观缓解率（ORR）和疾病控制率（DCR）（P<0.05），但降低了患者疾病进展（PD）发生率（OR=0.54 95%CI 0.29-0.99，P=0.05）；亚组分析显示剂量密集化疗延长老年患者（≥60岁）、FIGO分期III-IV期患者PFS（P<0.05）；安全性分析显示，剂量密集化疗增加3级以上贫血（OR=2.35，95%CI 1.38-3.99，P=0.002）、腹泻（OR=1.74，95%CI 1.01-2.74，P=0.02）发生率，其他3级以上不良反应均未见统计学差异（P>0.05）。结论：剂量密集化疗未改善原发上皮性卵巢癌患者PFS、OS、ORR、DCR和生存率，并增加了患者3级以上贫血、腹泻发生率，但延长老年及晚期患者PFS，降低PD发生率。     

EGFR-TKI联合化疗对比EGFR-TKI单药一线治疗EGFR敏感突变晚期非小细胞肺癌患者疗效的Meta分析北大核心CSCD

目的 :探讨表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)联合化疗治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者的临床价值。方法:检索PubMed、EMBASE和Web of Science等数据库从建库起到2017年公开发表的关于EGFR-TKI联合化疗对比EGFR-TKI单药一线治疗EGFR突变NSCLC的Ⅱ/Ⅲ期随机对照临床试验研究,并进行Meta分析。主要研究终点为无进展生存期(progression-free survival,PFS),次要研究终点为客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)和安全性。结果:纳入相关文献4篇,共353例患者。与EGFR-TKI单药相比,EGFR-TKI联合化疗可有效延长患者的PFS[风险比(hazard ratio,HR)=0.65,95%可信区间(condence interval,CI):0.50～0.84,P=0.001]。亚组分析结果显示,EGFR-TKI联合化疗组中EGFR突变亚型为Del19和L858R、年龄≥65岁、体力状况(performance status,PS)评分为1、女性和不吸烟的患者较EGFR-TKI单药组的PFS显著获益(P值均<0.05)。EGFR-TKI联合治疗组与EGFR-TKI单药组间ORR和DCR的差异均无统计学意义[相对危险度(relative risk,RR)=1.07,95%CI:0.94～1.22,P=0.282;RR=1.02,95%CI:0.96～1.08,P=0.531]。EGFR-TKI联合化疗可引起更多的乏力、恶心和中性粒细胞数减少(RR=2.64,95%CI:1.32～5.25,P=0.006;RR=6.87,95%CI:3.06～15.45,P<0.001;RR=10.02,95%CI:3.18～31.55,P<0.001)。2组患者间3级以上不良发应发生率的差异无统计学意义(P值均>0.05)。结论:与EGFR-TKI单药相比,EGFR-TKI联合化疗一线治疗EGFR基因突变NSCLC患者的PFS显著延长,且不良反应可耐受。     

EGFR-TKI联合化疗与单用化疗治疗晚期非小细胞肺癌有效性和安全性的Meta分析

摘 要：［目的］ 系统评价表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKI)联合化疗与单用化疗治疗晚期非小细胞肺癌有效性和安全性。［方法］ 计算机系统检索、搜集EGFR-TKI联合化疗对比单用化疗药治疗晚期NSCLC的相关随机对照试验(randomized controlled trails,RCTs)。提取客观反应率(objective response rate,ORR)、无进展生存期(progression-free survival,PFS)、总生存期(overall survival,OS)和不良反应(adverse events,AEs)等数据。［结果］ 共纳入15项研究。与单用化疗相比,EGFR-TKI联合化疗可显著提升晚期NSCLC患者的PFS(HR=0.73,95%CI：0.62~0.86,P=0.0002),并有延长OS 的趋势(HR=0.92,95%CI：0.86~1.00,P=0.05)。EGFR-TKI联合化疗的间插给药方式可显著性提升晚期NSCLC患者的PFS(HR=0.59,95%CI：0.51~0.68,Ｐ<0.00001)和OS (HR=0.84,95%CI：0.72~0.99,Ｐ=0.03)。此外,在EGFR敏感突变的患者中,EGFR-TKI联合化疗与单用化疗相比可显著性延长PFS(HR=0.38,95%CI：0.17~0.87,Ｐ=0.02)和OS (HR=0.45,95%CI：0.27~0.75,Ｐ=0.002)。［结论］　EGFR-TKI联合标准化疗是EGFR敏感突变的晚期NSCLC患者的一种极具潜力的治疗方案。此外,间插的治疗方式较同步的治疗方式更好,值得临床推广。     

贝伐单抗联合紫杉类化疗方案治疗HER-2阴性转移性乳腺癌的疗效评估:一项Meta分析

目的:采用Meta分析方法系统性评估贝伐单抗联合紫杉类化疗药物对HER-2阴性转移性乳腺癌的治疗效果。方法:电子计算机检索自建库至2020年12月发表的有关贝伐单抗联合紫杉类药物治疗HER-2阴性转移性乳腺癌的文章。根据制定的纳入和排除标准对文献进行筛选以及质量评价,然后提取研究数据。选择PFS、OS、ORR以及1年生存率（1y SR）作为主要疗效结局指标,采用Stata软件对合并效应量风险比率（hazard ratio,HR）和相对危险度（relative ratio,RR）进行Meta合并分析,按照研究类型进行亚组分析。发表偏倚利用漏斗图法以及Egger检验进行定性和定量评估。结果:初检文献849篇,最终纳入9篇文献进入Meta分析,研究共包含患者6 242例,其中贝伐单抗联合紫杉组3 555例,紫杉单药组2 687例。文献质量评价均为中等或高等质量。Meta合并结果显示,贝伐单抗联合紫杉方案对比紫杉单药能够显著提升PFS（HR=0.65,95%CI 0.55~0.77,Z=5.01,P＜0.001）、ORR（RR=1.59,95%CI 1.44~11.74,Z=9.61,P＜0.001）以及1y SR（RR=1.11,95%CI 1.08~1.15,Z=6.26,P＜0.001）,但在OS方面的优势不具有显著统计学意义（HR=0.83,95%CI 0.69~1.00,Z=2.0,P＜0.045）。结论:贝伐单抗联合紫杉类治疗方案,相比紫杉单药化疗方案可以明显提升PFS、ORR以及1年生存率,但并不能显著增加OS。因此,在临床实践中,应当谨慎选择化疗方案。     

贝伐珠单抗联合一线化疗晚期转移性结直肠癌的临床观察

目的：观察贝伐珠单抗联合一线化疗对晚期结直肠癌（metastatic colorectal cancer, mCRC）的疗效和毒副作用。方法30例经组织或细胞病理学证实的 mCRC 患者接受贝伐珠单抗与一线化疗药物联合治疗。贝伐珠单抗剂量为5 mg／kg 每2周重复,或7．5 mg／kg 每3周重复。一线化疗方案：18例联合 L-OHP 为主方案（FOLFOX 方案或者 CapeOx 方案）,12例联合 CPT-11为主方案（FOLFIRI方案）。评估疗效和不良反应并随访生存信息。结果30例中无 CR 患者,PR 15例（50．0％）,SD 10例（33．3％）,PD 5例（16．7％）;客观有效率50．0％,疾病控制率83．3％;中位无进展生存时间为10．809个月（95％CI：4．079～15．921）。贝伐珠单抗相关不良反应主要为高血压3例、鼻衄1例、蛋白尿1例。另有2例出现血液性毒性,考虑和化疗相关,接受 CPT-11方案者中4例出现迟发型腹泻。但上述副反应程度较轻,经对症处理后均可缓解,未影响治疗。结论贝伐珠单抗联合一线化疗对 mCRC 的疗效确切,不良反应发生率低、程度较轻,患者耐受性可,是mCRC一线治疗的理想选择。     

Analyses of Multiple Factors for Determination of “Selected Patients” Who Should Receive Rechallenge Treatment in Metastatic Colorectal Cancer: a Retrospective Study from Turkey

Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients withmetastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewedour registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatinbasedregimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who receivedirinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-linetherapy. These patients were selected from the database of Turkish mCRC registry archives between October2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overallsurvival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. Themedian duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up.In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line.Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factorseffecting survival (PFS and OS) were only being PFS after first-line chemotherapy ≥12 months (p=0.007, 95%CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: Thisstudy indicates that rechallenge treatment could be a good option as a third or later line therapy in patients whohad ≥12 months PFS onreceiving first line therapy.     

Genetic variants in CCL5 and CCR5 genes and serum VEGF-A levels predict efficacy of bevacizumab in metastatic colorectal cancer patients

Early VEGF-A reduction (EVR) by targeting abundant VEGF-A is a potential predictive marker of bevacizumab (BEV). The CCL5/CCR5 axis modulates VEGF-A production via endothelial progenitor cells migration. We tested whether genetic polymorphisms in the CCL5/CCR5 pathway could predict efficacy of BEV in patients with metastatic colorectal cancer (mCRC) in a first-line setting. Genomic DNA was extracted from 215 samples from three independent cohorts: 61 patients receiving FOLFOX+BEV (evaluation cohort); 83 patients receiving FOLFOX (control cohort); 71 patients receiving FOLFOX/XELOX+BEV (exploratory cohort) for validation and serum biochemistry assay (n = 48). Single nucleotide polymorphisms of genes in the CCL5/CCR5 pathway were analyzed by PCR-based direct sequencing. Considering the unbalanced distribution of patient baseline characteristics between the evaluation and control cohorts, propensity score matching analysis was performed. Serum VEGF-A levels during treatment were measured using ELISA. Among the evaluation and control cohorts, patients with any CCL5 rs2280789 G allele had longer progression-free survival (PFS) and overall survival (OS) when receiving FOLFOX+BEV than FOLFOX (PFS: 19.8 vs. 11.0 months, HR 0.44, 95%CI: 0.24–0.83, p = 0.004; OS: 41.8 vs. 24.5 months, HR: 0.50, 95%CI: 0.26–0.95, p = 0.024). No significant difference was shown in patients with the A/A variant. In the exploratory cohort, CCL5 rs2280789 G alleles were associated with higher VEGF-A levels at baseline and a greater decrease in VEGF-A levels at day 14 compared to the A/A variant. CCL5 and CCR5 impact the angiogenic environment, and the genotypes in CCL5/CCR5 genes may identify specific populations who will benefit from BEV in first-line treatment for mCRC.     

Post-induction Strategies in Metastatic Colorectal Cancer Patients Treated With First-Line Anti-EGFR-Based Treatment: A Systematic Review and Meta-Analysis

Few data from randomized clinical trials (RCTs) investigating the efficacy of post-induction strategies after the first-line treatment with anti-Epidermal Growth Factor Receptor (EGFR) in patients with metastatic colorectal cancer (mCRC) are available. A systematic review and metanalysis might therefore be useful to highlight and even strengthen these data. A literature search in Pubmed, Embase, American Society of Clinical Oncology (ASCO) Annual Meetings, ASCO Gastrointestinal Symposia, and European Society for Medical Oncology (ESMO) Congresses was performed. The search included RCTs of patients with mCRC treated with an initial period of cytotoxic chemotherapy (CT) in association with anti-EGFR (ie, panitumumab or cetuximab) as first-line regimen, and then switched to one of the following strategies: observation; maintenance with anti-EGFR, fluoropyrimidine (FP), or both; or continuing the induction regimen until disease progression or unacceptable toxicity. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the Mantel–Haenszel method fixed-effect model or the DerSimonian-Laird method random-effect model according to heterogeneity (I²). Analysis was performed on June 9, 2021. 7 studies (all phase II trials), including 1038 patients, were considered eligible for the meta-analysis. In all studies, CT (induction or maintenance with FP) + anti-EGFR until disease progression or unacceptable toxicity prolonged OS (HR = 0.72 [95%CI 0.61-0.86]; P < .01) and PFS (HR = 0.76, 95%CI 0.68-0.85; P < .01) compared to other agents (FP ± bevacizumab) or observation. Subgroup analyses for OS and PFS were performed according to type of maintenance therapy (containing or not containing single-agent anti-EGFR). Within patients evaluable for OS, CT + anti-EGFR combinations continued until disease progression were able to decrease the risk of death by 32% (HR 0.68; 95% CI 0.56-0.84; P < .01) and the risk of progression by 25% (HR 0.75; 95% CI 0.65-0.85; P < .01) over no maintenance or maintenance with anti-EGFR alone. Conversely, combination of CT + anti-EGFR were no better over anti-EGFR with FP in term of OS (HR = 0.81 [95%CI 0.60-1.09]; P = .17) and PFS (HR = 0.81 [95% 0.64, 1.01]; P = .06). Maintenance treatment with anti-EGFR + FP might be regarded as the better option following anti-EGFR based induction treatment in RAS wild-type mCRC, in terms of efficacy. This effect might be particularly amplified in left-sided BRAF wild-type mCRC patients. A higher level of evidence coming from phase III trials is auspicable.     

Differential Efficacy of Targeted Monoclonal Antibodies in Left-Sided Colon and Rectal Metastatic Cancers

BackgroundThe recommended first-line chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) is bevacizumab (BEV)-containing therapy for right-sided colon cancer (R) and antiepidermal growth factor receptor antibody (anti-EGFR)-containing therapy for left-sided colon cancer (L) or rectal cancer (RE). However, anatomical or biological heterogeneity reportedly exists between L and RE. Therefore, we aimed to compare the efficacies of anti-EGFR and BEV therapies for L and RE, respectively.MethodsWe retrospectively reviewed 265 patients with KRAS (RAS)/BRAF wild-type mCRC treated with fluoropyrimidine-based doublet chemotherapy plus anti-EGFR or BEV as the first-line treatment at a single institution. They were divided into 3 groups: R, L, and RE. Overall survival (OS), progression-free survival (PFS), objective response rate, and conversion surgery rate were analyzed.ResultsForty-five patients had R (anti-EGFR/BEV: 6/39), 137 patients had L (45/92), and 83 patients had RE (25/58). In patients with R, both median (m) PFS and OS were superior with BEV therapy (mPFS, anti-EGFR vs. BEV: 8.7 vs. 13.0 months, hazard ratio [HR]: 3.90, P = .01; mOS, 17.1 vs. 33.9 months, HR: 1.54, P = .38). In patients with L, better mPFS and comparable mOS with anti-EGFR therapy were observed (mPFS, 20.0 vs. 13.4 months, HR: 0.68, P = .08; mOS, 44.8 vs. 36.0 months, HR: 0.87, P = .53), whereas, in patients with RE, comparable mPFS and worse mOS with anti-EGFR therapy were observed (mPFS, 17.2 vs. 17.8 months, HR: 1.08, P = .81; mOS, 29.1 vs. 42.2 months, HR: 1.53, P = .17).ConclusionsEfficacies of anti-EGFR and BEV therapies may differ between patients with L and RE.     

脑转移瘤治疗模式Meta分析与评价

目的:应用Meta分析的方法探讨脑转移瘤的最佳治疗模式。方法:以中英文关键词检索Cochrane、PubMed、ASCO、ESMO、中国生物医学文献数据库、万方数据库、CNKI,检索时限为自各数据库建库起至2013年12月30日。按照jadad评分评价文献质量,采用RevMan5.0软件完成统计分析。结果:综合治疗方式与单一治疗相比可以明显提高脑转移患者的半年生存率（RR=0.75,95%CI:0.66-0.85,P<0.00001）。综合治疗组中,3种治疗方式联合与2种治疗方式联合相比脑转移患者的半年生存率明显提高（RR=0.59,95%CI:0.47-0.74,P<0.00001）。全身+局部治疗方式与局部治疗相比可以提高脑转移患者的半年生存率（RR=0.80,95%CI:0.67-0.96,P=0.02）。全身+局部联合治疗方式与全身治疗相比脑转移患者的半年生存率     

XELOX Plus Bevacizumab vs. FOLFIRI Plus Bevacizumab Treatment for First-line Chemotherapy in Metastatic Colon Cancer: a Retrospective Study of the Anatolian Society of Medical Oncology

Background: XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev)treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this studywas to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC. Materialsand Methods: A total of 409 patients with mCRC who received chemotherapy were included and divided into 2groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made interms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity. Results:Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%) , stable disease in 88 (29.5%)and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively.Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months,95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) forGroup 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4%in Group 1 and 26.1% in Group 2 (p<0.001). Conclusions: First-line XELOX-Bev is more effective with a betterresponse rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.     

比较吉非替尼与化疗一线治疗晚期非小细胞肺癌的Meta分析

目的 评价吉非替尼对比以铂类为基础的联合化疗一线治疗晚期非小细胞肺癌（NSCLC）的疗效与安全性。方法 检索PubMed、EMbase、中国生物医学文献数据库和中国知网等数据库,纳入吉非替尼对比铂类联合第3代化疗药物一线治疗晚期NSCLC的随机对照研究,检索时间截止于2012年3月,采用Stata 10.0软件进行Meta分析。结果 最终纳入4项研究,共1926例患者。在表皮生长因子受体（EGFR）突变阳性的人群中,吉非替尼在无进展生存期（HR=0.43,95％CI：0.32～0.58,P＜0.001）和有效率（71.5％ vs.38.1％,OR=4.04,95％CI：2.90～5.61,P＜0.001）方面均优于化疗组,在总生存期方面两组差异无统计学意义（HR=0.93,95％CI：0.75～1.15,P=0.492）。在安全性方面,吉非替尼主要为皮疹、腹泻和肝功能损害;化疗为中性粒细胞减少、血小板减少和贫血。结论 吉非替尼一线治疗晚期NSCLC具有一定优势,可作为EGFR敏感突变者的一线用药选择。