贝伐珠单抗序贯联合mFOLFOX或FOLFIRI方案治疗转移性结直肠癌的临床疗效观察

目的:探讨贝伐珠单抗联合mFOLFOX或FOLFIRI方案作为一线治疗,进展后相互转换为二线治疗在转移性结直肠癌治疗中的真实疗效对比。方法:选取我院于2017年01月至2021年06月收治的101例晚期结直肠癌患者,采取贝伐珠单抗联合mFOLFOX或FOLFIRI方案作为一线治疗,进展后相互转换为二线治疗,观察临床疗效及不良反应情况。结果:贝伐珠单抗先联合mFOLFOX后FOLFIRI组(以下称先mFOLFOX组/pre mFOLFOX)的一线ORR(objective response rate)为44.2%,DCR(disease control rate)为86.5%;二线ORR为24%,DCR为60%。贝伐珠单抗先联合FOLFIRI后mFOLFOX组(以下称先FOLFIRI组/pre FOLFIRI)的一线ORR为42.9%,DCR为81.6%;二线ORR为29.2%,DCR为62.5%。两组间的一/二线ORR及DCR差异均未达统计学意义。Kaplan-Meier分析显示先mFOLFOX6组与先FOLFIRI组的中位PFS(progression-free survival)-...     

贝伐珠单抗联合mFOLFOX6治疗转移性结直肠癌的临床疗效及左右半结肠癌的疗效差异

目的:观察贝伐珠单抗联合mFOLFOX6对比mFOLFOX6治疗晚期转移性结直肠癌的疗效及不良反应,并探索性地分析了左右半结肠癌的疗效差异性。方法:选取2017年1月至2018年8月在江门市中心医院肿瘤科确诊的72例晚期转移性结直肠癌患者,贝伐珠单抗+mFOLFOX6组33例,mFOLFOX6组39例,分析两组的治疗效果、中位PFS、不良反应,并分析不同治疗方案对左右半结肠癌疗效的影响。 结果:贝伐珠单抗+mFOLFOX6组ORR为45.5%,DCR为84.8%;mFOLFOX6组ORR为38.5%,DCR为79.5%。Kaplan-Meier分析显示mFOLFOX6组与贝伐珠单抗+mFOLFOX6组的中位PFS分别为6.2个月和7.7个月（P=0.06）。COX多因素分析结果显示贝伐珠单抗+mFOLFOX6组及mFOLFOX6组的PFS差异有统计学意义（P=0.024）,治疗线数对PFS的影响未达统计学差异（P=0.059）。Kaplan-Meier分析显示贝伐珠单抗+mFOLFOX6组中右半结肠癌的PFS为6.9个月,左半结肠癌的PFS为8.1个月（P=0.538）;mFOLFOX6组中右半结肠癌的PFS为6.37个月,左半结肠癌的PFS为6.2个月（P=0.209）。两组的不良反应主要为胃肠道反应、骨髓抑制及神经毒性。与贝伐珠单抗相关的不良反应主要为高血压、蛋白尿及血栓形成,除1例高血压为Ⅲ级外,其余均为Ⅰ-Ⅱ级。结论:贝伐珠单抗+mFOLFOX6治疗晚期转移性结直肠癌患者疗效好,不良反应可耐受,对左半结肠癌的PFS有获益的趋势。     

FOLFOX联合贝伐珠单抗或西妥昔单抗一线治疗野生型KRAS晚期结直肠癌的临床疗效

目的 :本研究旨在比较贝伐珠单抗联合FOLFOX方案与西妥昔单抗联合FOLFOX方案一线治疗野生型KRAS晚期结直肠癌的疗效、不良反应和生存情况。方法 :研究对象为2008年1月—2014年2月在中国人民解放军总医院肿瘤内科住院的72例野生型KRAS晚期结直肠癌患者,分别接受FOLFOX方案(28例)、贝伐珠单抗联合FOLFOX方案(17例)和西妥昔单抗联合FOLFOX方案(27例)的一线化疗。化疗3个周期后,评价近期疗效;观察化疗不良反应。对所有患者进行随访,计算无进展生存期(progression-free survival,PFS)。结果 :FOLFOX组客观有效率(objective response rate,ORR)为14.3%,疾病控制率(disease control rate,DCR)为75.0%,中位PFS为8.0个月;贝伐珠单抗联合FOLFOX组ORR为64.7%,DCR为94.1%,中位PFS为10.0个月;西妥昔单抗联合FOLFOX组ORR为59.3%,DCR为92.6%,中位PFS为9.2个月。FOLFOX组ORR与贝伐珠单抗联合FOLFOX组和西妥昔单抗联合FOLFOX组比较,差异均有统计学意义(χ2=12.101,P=0.000 5;χ2=12.014,P=0.000 5)。3组DCR和中位PFS的差异均无统计学意义(P>0.05)。结论 :贝伐珠单抗或西妥昔单抗联合FOLFOX方案可提高野生型KRAS晚期结直肠癌患者的ORR和DCR,延长PFS;并且,这2种方案的疗效相当,不良反应均较小,耐受性也较好。     

贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌患者的疗效及预后分析

  目的  探讨贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌（non-squamous non-small cell lung cancer,NSNSCLC）患者的疗效和安全性,分析影响预后的因素。  方法  回顾性分析2013年2月至2017年6月北京胸科医院收治的41例复治晚期NSN? SCLC患者的病例资料。其中腺癌38例,其他病理类型3例。19例患者为二线治疗,22例患者为二线以上治疗。表皮生长因子受体（epidermal growth factor receptor,EGFR）突变阳性18例,突变阴性23例。评价贝伐珠单抗联合化疗的疗效和安全性,对可能影响预后的因素进行单因素和多因素分析。  结果  所有患者均接受化疗联合贝伐珠单抗的治疗,化疗的平均周期数为3.1个,贝伐珠单抗治疗的平均周期数为5.0个。41例患者均可评价疗效。全组患者客观缓解率（objective response rate,ORR）为12.2%,疾病控制率（disease control rate,DCR）为82.9%。二线治疗与二线以上治疗的患者疗效接近,ORR分别为10.5%、13.6%（P=0.572）,DCR分别为89.5%和77.3%（P=0.271）,差异无统计学意义。中位无进展生存期（progression-free survival,PFS）和中位总生存期（overall survival,OS）分别为4.6个月（95%CI:3.619~5.581）、11.9个月（95%CI:9.797~14.003）。单因素分析提示EGFR突变、贝伐珠单抗治疗周期数 > 4个及女性患者获得更长的生存（χ2=19.673,P < 0.001;χ2=6.820,P=0.009;χ2=6.374,P=0.012）。多因素分析显示,EGFR突变状态、贝伐珠单抗治疗周期数为影响患者预后的独立危险因素（HR=0.129,P=0.001;HR=0.336,P=0.012）。常见的不良反应有骨髓抑制、出血、高血压、蛋白尿等,多数为1~2级。  结论  贝伐珠单抗联合化疗对复治晚期NSNSCLC患者疗效确切,不良反应可耐受,EGFR突变阳性、贝伐珠单抗使用4个周期以上的患者预后较好。      

贝伐珠单抗联合FOLFOX或FOLFIRI方案治疗转移性结直肠癌的临床研究

目的 观察贝伐珠单抗联合FOLFOX或FOLFIRI方案用于转移性结直肠癌一线及二线治疗的临床疗效和毒副反应。方法 回顾性分析2005年11月至2012年8月接受贝伐珠单抗联合FOLFOX或FOLFIRI方案作为一线及二线治疗的57例转移性结直肠癌患者的临床资料。采用RECIST 1.1版评价疗效,用NCI-CTC 3.0版评价不良反应,用Kaplan-Meier法进行生存分析。结果 57例结直肠癌患者中,19例（33.3％）获PR,28例（49.2％）获SD,有效率（RR）为33.3％,疾病控制率（DCR）为82.5％。贝伐珠单抗联合化疗用于一线与二线治疗患者的RR或DCR差异均无统计学意义（P＞0.05）;贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的RR或DCR差异均无统计学意义（P＞0.05）。57例患者的无进展生存期（PFS）及总生存期（OS）分别为8.83个月及14.80个月。一线与二线治疗及贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的中位PFS或OS差异均无统计学意义（P＞0.05）。主要不良反应包括白细胞减少、血小板减少及恶心呕吐。贝伐珠单抗相关的不良反应主要包括高血压3例,蛋白尿1例,鼻衄2例,均为1～2级,药物可以控制。结论 贝伐珠单抗联合化疗治疗转移性结直肠癌能够提高治疗疗效,不良反应可以耐受。     

贝伐珠单抗联合双周方案一线治疗晚期大肠癌的疗效及与K-ras基因的关系

目的:探讨贝伐珠单抗（BEV）联合双周方案一线治疗晚期大肠癌的临床疗效及与K-ras基因的关系。方法:收集2008年1月至2014年2月解放军总医院收治、经病理确诊的46例K-ras基因状态明确的晚期大肠癌患者临床资料,其中K-ras野生型23例、K-ras突变型23例;回顾性分析了BEV联合FOLFIRI（20例）或FOLFOX（26例）方案在一线治疗晚期大肠癌中的疗效及毒副反应的情况,并分析K-ras基因突变与疗效的关系。结果:46例均可评价近期疗效,总ORR为39.1%,总DCR为91.3%,总中位PFS为7.5个月。以化疗方案分组,其中FOLFIRI+BEV组ORR为30.0%,DCR为95.0%,中位PFS为8.1个月;FOLFOX+BEV组ORR为46.2%,DCR为88.5%,中位PFS为6.5个月。以K-ras基因状态分组,K-ras突变组ORR为30.4%,DCR为91.3%,中位PFS为6.2个月;K-ras野生组ORR为47.8%,DCR为91.3%,中位PFS为9.9个月。以上差异均无统计学意义（P＞0.05）。结论:虽然K-ras突变组在近期、远期疗效低于K-ras野生组,但在两组中均可见应用BEV能获益,同时再次证实K-ras基因突变是患者预后不良因素之一,但不是BEV应用的禁忌症;在化疗方案方面,BEV联合FOLFIRI或FOLFOX标准双周方案可提高化疗的ORR及DCR,且毒副反应小,安全性较好。     

含贝伐珠单抗维持治疗晚期结直肠癌患者疗效与安全性的Meta分析

目的 系统评价含贝伐珠单抗不同联合方案治疗晚期结直肠癌的疗效与安全性。方法 计算机检索PubMed、EMbase、Web of Science、Cochrane Library 数据库截至2017年7月31日有关贝伐珠单抗维持治疗晚期结直肠癌的随机对照试验。按纳入排除标准筛选文献、资料提取和评价质量,采用RevMan 5.3 软件进行Meta 分析。 结果 共纳入8项研究,2 644例晚期结直肠癌患者。Meta分析显示,贝伐珠单抗维持治疗组（包括单药和联合化疗）前者无疾病进展生存期（PFS）和总生存期（OS）均优于无治疗组（HR=0.65,95% CI：0.53~0.78,P<0.001;HR=0.83,95% CI：0.71~0.98,P=0.020）,但前者3~4级感觉神经障碍及高血压发生率高于后者（P=0.001,0.008）。贝伐珠单抗维持治疗组与持续治疗组对比,两者的PFS和OS相当（HR=1.05,95% CI：0.56~1.71,P=0.830;HR=1.11,95% CI：0.92~1.35,P=0.270）,而后者3~4级感觉神经障碍、疲乏和手足综合征明显高于前者（P＜0.001,0.020,0.040）。与单药贝伐珠单抗组比较,贝伐珠单抗抗抗联合厄洛替尼组能改善PFS和OS（HR=0.81,95% CI：0.67~0.96,P=0.020;HR=0.81,95% CI：0.67~0.99,P=0.040）,但贝伐珠单联合厄洛替尼组3~4级皮疹发生率明显高于单药贝伐珠单抗组（P<0.001）。结论 贝伐珠单抗单药、联合低毒化疗药物或厄洛替尼,均可改善晚期结直肠癌患者PFS和OS,患者可耐受,贝伐珠单抗维持治疗可作为晚期结直肠癌维持阶段的优选治疗方案。     

贝伐株单抗联合化疗在HER2阴性进展期乳腺癌治疗中的疗效和安全性分析

目的：观察贝伐珠单抗（BV）联合化疗治疗HER2阴性进展期乳腺癌的疗效和安全性。方法回顾性分析接受贝伐株单抗治疗的15例进展期乳腺癌患者的临床资料,按照实体肿瘤疗效评价标准（RECIST 1.1）和美国国立癌症研究所不良反应事件通用术语标准评价疗效和不良反应,每2个月评估疗效,主要观察终点是无进展生存期（progression free survival,PFS）,每个周期评价不良反应。结果15例患者的中位PFS为4个月;治疗10个周期以上的患者为4例,6个周期以上者3例,其余8例均不足4个周期;15例患者均可评价疗效,5例（33.33%）PR中4例伴胸壁转移;5例SD（33.33%）,5例PD（33.33%）;主要不良反应为高血压4例、少量鼻出血3例、蛋白尿2例、贫血2例、血小板减少2例,经对症治疗后均好转,4例停药。结论贝伐珠单抗联合化疗作为二线及以上方案治疗进展期乳腺癌仍有一定疗效,对于伴胸壁转移的患者疗效尤其显著,不良反应可耐受。     

贝伐珠单抗联合化疗治疗胃肠肿瘤的不良事件观察

  目的  观察贝伐珠单抗（Bevacizumab,AVASTIN,Bev）与化疗药物联合治疗胃肠道肿瘤患者的不良事件,以便合理、安全的使用贝伐珠单抗,避免严重不良事件的发生。  方法  回顾性分析贝伐珠单抗（Bev）联合常规化疗治疗胃肠肿瘤77例,收集整理患者既往史,治疗前及治疗开始直至停止治疗后8周或死亡期间症状、体征和实验室检查,分析其在胃肠肿瘤患者治疗中的安全性。  结果  患者均为不能手术的局部进展期或转移性胃癌和结直肠癌,其中结直肠癌65例,胃癌12例,均采用贝伐珠单抗联合化疗。男性36例,女性41例,中位年龄49岁。77例患者中不良事件发生率为89.6%（69/77）,3/4级不良事件（adverse even,AE）及严重不良事件（serious adverse even,SAE）发生率为26.0%（20/77）。分层分析不同情况下3/4级AE和SAE发生率,高龄组（≥65岁）为44.4%（4/9）,低龄组（< 65岁）为23.5%（16/68）;男性为25%（9/36）,女性为26.8%（11/41）;一线使用化疗联合贝伐珠单抗患者组为30.6%（11/36）,二线及以上使用化疗联合贝伐珠单抗为22.0%（9/41）,均无统计学差异。贝伐珠单抗联合两药化疗方案,其AE均以以血液学毒性和消化道反应（恶性、呕吐）为主,发生率50%~60%。贝伐珠单抗联合单药化疗AE发生率5%~8%。高血压、蛋白尿、出血及伤口愈合不良均为偶发、轻度。SAE 1例。  结论  贝伐珠单抗联合化疗治疗胃肠恶性肿瘤AE发生率无明显增加,性别、年龄以及使用贝伐珠单抗的时机（一线或二线及以上使用）等,其不良事件的发生率均无明显差异,贝伐珠单抗联合化疗治疗胃肠肿瘤患者耐受性良好。      

贝伐珠单抗联合化疗治疗KRAS突变型晚期左、右半结肠癌疗效的对比分析

目的:对比分析姑息一线应用贝伐珠单抗联合化疗治疗KRAS突变型晚期左、右半结肠癌的临床疗效。方法:回顾性分析我院于2016年09月至2020年09月收治的83例一线应用贝伐珠单抗联合化疗治疗KRAS突变型晚期左、右半结肠癌患者,比较KRAS突变型左、右半结肠癌患者的临床特征、客观缓解率（ORR）、疾病控制率（DCR）、无进展生存时间（PFS）、18个月生存率、总生存时间（OS）。结果:KRAS突变型晚期右半结肠癌（RSCC）患者合并不完全肠梗阻及体重减轻＞5 kg所占比例更高（P=0.369、P=0.009）,KRAS突变型晚期左半结肠癌（LSCRC）患者更易合并中重度以上的贫血（P=0.154）。KRAS突变型LSCRC患者发生腹腔种植转移及远处器官转移的患者比例高于RSCC患者（P＞0.05）。KRAS突变型LSCRC患者与RSCC患者ORR分别为29.3%和28.6%（P=0.944）,DCR分别为87.8%和90.5%（P=0.696）。18个月生存率LSCRC组为80.05%,RSCC组为76.2%,差异无统计学意义（P=0.635）。KRAS突变型LSCRC患者中位 PFS差于RSCC患者（8个月 vs 9.8个月,P=0.004）,KRAS突变型LSCRC患者中位OS优于KRAS突变型RSCC患者中位OS（22.8个月 vs 21个月,P=0.001）。结论:姑息一线应用贝伐珠单抗联合化疗治疗KRAS基因突变型mCRC患者,左、右半结肠癌的远期疗效存在差异。     

曲妥珠单抗联合FLOT方案围手术期治疗可手术HER-2阳性进展期胃癌的疗效和安全性

目的:评估曲妥珠单抗联合FLOT方案作为可手术HER-2阳性进展期胃癌围手术期治疗的有效性和安全性。方法:FLOT方案具体为:多西他赛50 mg/m2,奥沙利铂85 mg/m2,亚叶酸钙200 mg/m2,5-FU 2 600 mg/m2（24小时持续静脉泵入）,第一日,2周重复,术前和术后各4周期,曲妥珠单抗具体为:首次剂量8 mg/kg,后续6 mg/kg,第1、22、43日,3周重复,术前和术后各3周期,手术与化疗间隔3周。主要观察患者的客观缓解率、疾病控制率、肿瘤退缩程度、安全性和总生存时间。结果:共有31例患者入组,中位随访时间24.5个月。通过治疗,疗效为CR、PR、SD和PD的患者分别为:5例(16.1%)、18例(58.1%)、5例(16.1%)和 3例(9.7%),ORR 为74.2%（23/31）,DCR 为90.3%（28/31）,R0切除率96.8%（30/31）。有5例(16.1%)患者获得TRG1a,8例(25.8%)患者获得TRG1b,均未见复发。最常见的3-4 级副作用为粒细胞缺乏症（19.4%）和呕吐(3.2%)。2年OS 78.6%。结论:曲妥珠单抗联合FLOT方案作为可手术HER-2阳性进展期胃癌围手术期的治疗具有很好的疗效和安全性。     

The efficacy of bevacizumab in Chinese patients with metastatic colorectal cancer and its effect in different line setting

Objective:We aimed to evaluate the ef ect of bevacizumab in the pal iative treatment of Chinese metastatic colorectal cancer (mCRC) and its ef icacy in dif erent lines. Methods:Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2005 to 2013 were recruited as the study group and control group. The endpoints were objective response rate (ORR), disease control rate (DCR), overal survival (OS) and progression free survival (PFS). The OS and PFS of first-, second-and third-line treatment groups were compared between study group and control group. Re-sults:The median PFS of the study and the control group were 8.2 months (7.0-9.4 months), 5.7 months (4.7-6.6 months), P=0.001;OS were 26 months (5.4-130.5 months), 18 months (16.6-19.4 months), P<0.001, respectively. The ORR and DCR of first-, second-and third-line were 30.3%(20/66), 20%(6/30), 17.6%(3/17) and 97%(64/66), 86.7%(26/30), 100%(17/17). In the first-line chemotherapy group, the OS of the study group and the control group were 22.9 (5.4-96.7) months and 18 (16.6-19.4) months (P<0.001);PFS were 9.4 (8.4-10.4) months and 5.7 (4.7-6.6) months (P<0.001), respectively. While in the second-and third-line setting, only OS were statistical y dif erent, PFS had no significant dif erence. Conclusion:The combination of bevacizumab and chemotherapy had a promising short-term and long-term ef icacy in Chinese mCRC patients than those without bevacizumab regimens, and the ef ect could be better reflected in the first-line treatment.     

Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial

BackgroundThe oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC.MethodsIn this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4–10 and 18–24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety.ResultsMedian overall treatment duration with any study drug was 9.9 months (range 0.6–19.6); median treatment duration with regorafenib was 7.7 months (range 0.1–19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications.ConclusionRegorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.ClinicalTrials.gov identifier: NCT01289821.     

Bevacizumab combined with chemotherapy in the second-line treatment of metastatic colorectal cancer: results from the phase II BEVACOLOR study

BackgroundThis prospective phase II study assessed the efficacy and safety of bevacizumab plus chemotherapy regimens commonly used in the second-line treatment of metastatic colorectal cancer (mCRC).MethodsPatients with mCRC who progressed or relapsed after first-line oxaliplatin-based or irinotecan-based treatment received bevacizumab 2.5 mg/kg/week plus chemotherapy until disease progression. The primary endpoint was disease-control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety.ResultsFifty-three patients (66% men; median age, 62 years old) received second-line bevacizumab plus folinic acid, fluorouracil, and irinotecan (FOLFIRI; 57%), folinic acid, fluorouracil, oxaliplatin (FOLFOX; 26%), irinotecan (15%), or capecitabine plus irinotecan (XELIRI; 2%). The DCR was 87% (95% CI, 77%-97%); ORR was 32% (95% CI, 19%-46%). Median PFS was 6.5 months (95% CI, 5.8-7.8 months) and median OS 19.3 months, (95% CI, 14.2-25.1 months).The most frequent grade 3/4 adverse events included neutropenia (21%), diarrhea (15%), asthenia, and vomiting (9% each). Five patients (9%) had grade 3/4 targeted toxicities: grade 3 hypertension (n = 2), grade 3 venous thromboembolism (n = 2), and grade 4 arterial thromboembolism (n = 1). None of these events led to death during the study.ConclusionBevacizumab plus standard second-line chemotherapy is highly active in patients with mCRC and has an acceptable safety profile.     

Randomized Phase II Open-Label Study of mFOLFOX6 in Combination With Linifanib or Bevacizumab for Metastatic Colorectal Cancer

BackgroundAlthough CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC.Patients and MethodsOne hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety.ResultsNo statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab.ConclusionCombining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.     

阿帕替尼治疗二线化疗失败的晚期卵巢癌的疗效和安全性评价

目的:评价甲磺酸阿帕替尼片治疗二线化疗失败的晚期上皮性卵巢癌患者的有效性与安全性。方法:研究共纳入20例患者,最终分析17例。入组患者口服阿帕替尼片,500 mg或250 mg 每日1次,连用28天为一个观察周期,治疗三个周期后行疗效评价。结果:治疗3个月后,PR占35.3%（6/17）,SD占11.8%（2/17）,ORR为35.3%,DCR为47.1%。起始剂量为500 mg组（ORR,30%;DCR,30%）及250 mg组（ORR,42.9%;DCR,71.4%）患者治疗效果比较无明显统计学差异。患者的中位PFS为2.2个月,中位OS为6.3个月。患者出现的最主要不良反应为高血压（70.6%）、手足综合征（52.9%）、口腔黏膜损伤（35.3%）。结论:针对二线以上化疗失败的晚期卵巢癌患者,阿帕替尼口服治疗具有一定的疗效,且安全性好,无严重不良反应。     

Equivalent efficacy study of QL1101 and bevacizumab on untreated advanced non-squamous non-small cell lung cancer patients: a phase 3 randomized,double-blind clinical trial

Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101, a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer (NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab, 15 mg/kg every 3-week for 6 cycles. This was followed by maintenance treatment with single agent QL1101 every 3-week. The primary end-point was objective response rate (ORR), with secondary end-points being progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs).Results:Of 675 patients, 535 eligible patients were randomized to the QL1101 group (n = 269) and bevacizumab group (n = 266). ORRs were 52.8% and 56.8%, respectively, for the QL1101 and bevacizumab groups, with an ORR hazard ratio 0.93 (95% confidence interval: 0.8–0131.1). The PFS, OS, DCR, and AEs were comparable between the 2 groups, which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.     

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)

BackgroundFOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab.Patients and methodsWJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396.ResultsAmong 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723–1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785–1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months.ConclusionFOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC.Clinical trials numberUMIN000001396.