PD-1/L1免疫检查点抑制剂用于EGFR-TKIs耐药后晚期非小细胞肺癌的疗效分析

目的 探讨PD-1/L1免疫检查点抑制剂用于EGFR-TKIs耐药后晚期非小细胞肺癌的疗效与安全性。方法 回顾性分析长征医院2019年1月至2021年1月期间收治的经一线EGFR-TKIs治疗失败后的Ⅳ期非小细胞肺癌患者。按照治疗方案分为3组：PD-1/L1抑制剂联合贝伐珠单抗联合化疗组、PD-1/L1抑制剂单药治疗组和抗血管生成药物联合化疗组，比较三组客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、无进展生存期(progression-free survival, PFS)及三组的不良反应(adverse events, AEs)的差异。结果 三组间ORR和DCR差异均无统计学意义。免疫四药联合组与免疫单药组相比，中位PFS(总体：6.2个月vs 3.2个月),差异具有统计学意义(P<0.001),而OS(总体：16.1个月vs 9.4月),差异不具有统计学意义(P=0.509)。免疫四药联合组与贝伐珠单抗联合化疗组比较，中位PFS(总体：6.2个月vs 4.0个月),差异具有统计学意义(...     

TACE联合索拉非尼治疗肝癌合并门静脉癌栓的临床疗效及安全性

目的评价经皮导管动脉化疗栓塞术(TACE)联合索拉非尼治疗原发性肝癌(HCC)伴门静脉癌栓(PVTT)的临床疗效及安全性。方法 2015年1月至2016年1月确诊为HCC合并PVTT患者60例,随机分为联合治疗组(n=30)和对照组(n=30)。联合治疗组采用TACE+索拉非尼治疗,对照组采用TACE治疗。用改良实体瘤疗效评价标准(mRECIST)评估疗效。随访观察总生存期(OS)、疾病进展时间(TTP)、疾病控制率(DCR)和毒副反应。结果治疗组DCR为60.0%,对照组DCR为36.7%,治疗组DCR和对照组DCR相比,差异具有统计学意义(P0.05),治疗组中位OS为10.3个月(95%CI:7.2～13.5),对照组患者OS为5.7个月(95%CI:4.5～6.8),治疗组DCR和对照组DCR相比,差异具有统计学意义(P0.05);治疗组中位TTP为5.5个月(95%CI:4.6～6.7),对照组中位TTP为3.0个月(95%CI:2.1～3.7),治疗组DCR和对照组DCR相比,差异具有统计学意义(P0.05)。两组TACE相关不良反应差异无统计学意义,治疗组出现4例索拉非尼相关严重毒副反应,但未出现药物相关死亡患者。结论 TACE联合索拉非尼治疗HCC合并PVTT总体生存期及疾病控制率明显优于单纯TACE治疗,且安全性良好。     

卡瑞利珠单抗联合化疗一线治疗晚期肺鳞癌的临床疗效分析

目的探讨卡瑞利珠单抗联合化疗一线治疗晚期肺鳞癌的疗效与安全性。方法回顾性分析2018年4月至2020年10月在郑州大学第一附属医院收治的78例驱动基因阴性的晚期肺鳞癌患者的临床资料。将39例卡瑞利珠单抗联合化疗的患者归为观察组,39例单纯化疗的患者归为对照组,比较两组客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)及两组的不良反应(adverse events,AEs)的差异。结果两组ORR、DCR差异无统计学意义(P>0.05)。观察组和对照组mPFS分别为8.00个月和5.30个月(P<0.05)。不良反应方面:与对照组相比,观察组除反应性毛细血管增生症(Reactive capillary hemangiomas,RCHs)外,未发现其它新增的不良反应,RCHs发生率约82.1%(P<0.001),但都是G1~G2级,在可控范围内。两组消化道反应、骨髓抑制、乏力、神经毒性等发生率差异均无统计学意义(P>0.05)。结论与单纯化疗相比,卡瑞利珠单抗联合化疗一线治疗晚期肺鳞癌,延长了患者的无进展生存期,不良反应可控。     

索拉非尼联合替吉奥或紫杉醇治疗原发性肝癌的临床疗效及安全性对比

目的比较索拉非尼联合紫杉醇或替吉奥治疗原发性肝癌的疗效和安全性。方法将120例原发性肝癌患者随机分为研究组(60例)和对照组(60例),分别进行索拉非尼联合紫杉醇、索拉非尼联合替吉奥治疗。随访两年,对两组患者的近期疗效指标包括完全缓解(CR)、部分缓解(PR)、病情稳定(SD)、疾病进展(PD)、临床控制率(DCR)、总有效率以及远期疗效指标如无进展生存期(PFS)和总生存期(OS)进行对比分析,观察两组的不良反应发生情况。结果研究组和对照组的平均治疗周期数分别为(2.8±0.3)和(3.3±0.2),差异无统计学意义(P0.05)。研究组CR、PR、SD、PD比例分别为0%、18.3%、41.7%、40.0%,对照组为0%、16.7%、46.7%、36.6%。研究组患者总有效率为18.3%,DCR为60.0%,对照组总有效率为16.7%,DCR为63.4%,两组比较差异无统计学意义(P0.05)。研究组和对照组患者中位OS分别为(14.5±2.6)个月和(14.9±2.0)个月,中位PFS分别为(6.3±0.5)个月和(6.8±1.1)个月,差异无统计学意义(P0.05)。研究组患者死亡率(65%)小于对照组(73.3%)。研究组发生Ⅲ~Ⅳ级毒性反应主要为AST增加(8.3%)、腹泻(5.0%)和手足皮肤反应(3.3%),共发生不良反应109例次。对照组发生Ⅲ~Ⅳ级毒性反应主要为AST增加(15.0%)、血小板减少(11.7%)、腹泻(10.0%)、手足皮肤反应(8.3%)和中性粒细胞减少(6.7%),共发生不良反应136例次。研究组的毒副反应发生率小于对照组,差异有统计学意义(P0.05)。结论索拉非尼联合紫杉醇治疗肝细胞癌(HCC)的安全性比索拉非尼联合替吉奥高,可以成为HCC患者临床治疗的一种有效选择,为HCC的综合治疗提供理论依据。     

索拉非尼治疗老年晚期肝癌的临床观察

目的观察索拉非尼治疗晚期肝癌(HCC)的有效性和安全性。方法 20例老年晚期HCC患者口服索拉非尼单药治疗(400mg,每日2次),至疾病进展或出现不可耐受的毒副反应,每6周按照RECIST标准(1.0版)进行疗效评价,按NCI-CTC(3.0版)评价毒副反应并动态监测甲胎蛋白(AFP)的变化和随访生存情况。结果在19例可评价的患者中获得SD12例,PD7例,疾病控制率(DCR)为63.2%,中位疾病进展时间(mTTP)为3.8个月(95%CI:2.54～5.06个月)中位总生存期(mOS)为6.0个月(95%CI:3.94～8.06个月),治疗前12例AFP高于正常,治疗后明显下降3例,稳定4例,升高5例。主要不良反应为手足皮肤反应、食欲下降和腹泻。结论索拉非尼治疗老年晚期肝癌有效毒副反应可耐受。值得进一步观察。     

TACE联合索拉非尼对不能手术切除肝细胞肝癌的疗效分析

目的分析经导管肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)联合索拉非尼对不能手术切除肝细胞肝癌(hepatocellular carcinoma,HCC)的疗效。方法选取海军总医院2008年10月-2010年10月收治的不能手术切除的HCC患者,共162例,按照随机数字表分为联合组及TACE组,各81例,分别接受TACE联合索拉非尼治疗及单纯TACE治疗,比较两组患者的疗效。结果联合组部分缓解11例,稳定65例,有效率93.8%,TACE组部分缓解7例,稳定42例,有效率60.5%,联合组治疗效果显著优于TACE组(P0.05);联合组生存质量改善36例,稳定26例,稳定及改善率76.5%,TACE组改善19例,稳定23例,稳定及改善率51.9%,联合组生存质量改善程度显著优于对照组(P0.05);两组患者治疗后丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)均显著升高,血清白蛋白(ALB)均无明显变化,两组患者治疗后ALT、TBIL及ALB水平差异无统计学意义(P0.05);两组不良反应发生率分别为80.2%、81.5%,差异无统计学意义(P0.05);联合组6个月、12个月生存率分别为77.8%、69.1%,TACE组分别为59.3%、50.6%,联合组生存率显著高于TACE组(P0.05)。结论 TACE联合索拉非尼较单纯TACE治疗具有更好的疗效,能够有效延长患者生存期、保证其生活质量,且不良反应耐受性好,为不能手术切除HCC的治疗提供了新的方法。     

自体细胞生物化疗在晚期非小细胞肺癌治疗中的临床应用

目的探讨树突状细胞(dendritic cells,DCs)和细胞因子诱导的杀伤细胞(cytokine-induced killers,CIKs)联合化疗对晚期非小细胞肺癌(NSCLC)患者的疗效。方法 DC-CIK细胞治疗联合化疗的ⅢB期、Ⅳ期非小细胞肺癌患者为治疗组,同期相同入组标准的单纯化疗者作为对照组。治疗组和对照组各40例,比较两组患者治疗前后外周血T细胞亚群、临床疗效、生活质量变化等。结果两组的一般资料基线水平一致。与对照组相比,治疗组T细胞亚群变化无统计学意义(P>0.05)。治疗组疾病控制率[DCR(90%)]明显高于对照组DCR(72.5%),差异具有统计学意义(P<0.05)。两组中位无进展生存期(progression free survival,PFS)分别为275 d vs.212 d,治疗组PFS长于对照组(P<0.05)。但两组间客观缓解率(objective response rate,ORR)、总生存期(overall survival,OS)无统计学意义(P>0.05)。治疗后生活质量(KPS)评分下降者,治疗组较对照组少(P<0.05),未见不可耐受不良反应。结论自体DC-CIK联合化疗的生物化疗模式,可提高晚期NSCLC患者疾病控制率、延长无进展生存期,改善患者生活质量。     

程序性细胞死亡受体1抑制剂联合仑伐替尼治疗晚期原发性肝癌的效果及不良反应

目的初步探索国产程序性细胞死亡受体1(PD-1)抑制剂联合仑伐替尼在晚期原发性肝癌治疗中的临床疗效及不良反应。方法回顾性分析2019年1月1日—2020年4月2日于首都医科大学附属北京地坛医院使用国产PD-1抑制剂联合仑伐替尼治疗的24例晚期肝癌患者的临床资料,其中卡瑞利珠单抗联合仑伐替尼治疗组15例,信迪利单抗联合仑伐替尼治疗组7例,特瑞普利单抗联合仑伐替尼组2例。随访患者,肝内病灶使用mRECIST标准、肝外转移灶采用RECIST1.1标准评价疗效。Kaplan-Meier法绘制生存曲线。结果24例肝癌患者中,11例疗效评价为部分缓解,7例疗效评价为疾病稳定,6例疗效评价为疾病进展,客观缓解率为45.8%,疾病控制率为75.0%。中位疾病进展时间为8.40个月(95%CI:6.89~9.91个月)。不良反应发生率为54.17%,最常见的不良反应为疲乏(29.17%)、高血压(25.00%)。结论PD-1抑制剂联合仑伐替尼治疗晚期肝癌临床效果显著,严重不良反应发生率低,是一种安全、有效的治疗方案。     

瑞戈非尼联合程序性死亡受体1抑制剂治疗难治性pMMR/MSS转移性结直肠癌的疗效和安全性

目的 观察瑞戈非尼联合程序性死亡受体1(PD-1)抑制剂治疗难治性pMMR/MSS转移性结直肠癌的临床疗效和安全性。方法 难治性pMMR/MSS转移性结直肠癌患者26例,均应用瑞戈非尼（80 mg、120 mg或160 mg,每日口服1次,连续用药21 d,停药7 d,28 d为一周期）联合PD-1抑制剂（替雷利珠单抗200 mg、特瑞普利单抗240 mg、卡瑞利珠单抗240 mg或信迪利单抗200 mg,均在第1天静脉输注,21 d为一周期）治疗,观察其临床疗效[疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）]及安全性（不良反应发生率）。结果 治疗后,26例难治性pMMR/MSS的转移性结肠癌的客观缓解率（ORR）为7.7%(2/26)、均为部分缓解（PR）,DCR为65.3%(17/26),PFS为3.5个月,OS为24.3个月。难治性pMMR/MSS转移性结肠癌肝转移患者和无肝转移患者的中位PFS分别为4.5、3.3个月,两者比较,χ2=0.447,P=0.504;中位OS分别为16.8、24.9个月,两者比较,χ2=0.115,P=0.735。瑞戈非尼80 mg...     

转移性结直肠癌治疗中贝伐单抗相关性高血压的发生及意义

目的:观察贝伐单抗治疗转移性结直肠癌(metastatic colorectal cancer,MCC)中高血压的发生情况,评价其对贝伐单抗疗效的预测价值.方法:回顾性分析我院使用贝伐单抗联合化疗治疗的MCC患者中,不良反应高血压的发生、治疗及转归.根据是否发生贝伐单抗相关性高血压把患者分为两组,比较两组疾病控制率(disease control rate,DCR)和无进展生存时间(progression-free survival,PFS).结果:40例MCC患者使用贝伐单抗联合化疗治疗,高血压发生的中位时间为38d,发生率为17.5%(7/40),3级高血压发生率为5.0%(2/40),无4-5级高血压发生,降压治疗后血压均可控制.与未发生高血压患者比较,发生高血压患者的DCR更高(85.8% vs 60.1%,P=0.439),PFS(13 mo vs 8 mo,P=0.191)更长但未达统计学差异.结论:高血压为贝伐单抗治疗MCC中常见不良反应,大多为轻-中度,降压治疗效果好,但高血压未能显示出对贝伐单抗疗效的预测作用.     

Comparison of the effects of lenvatinib and sorafenib on survival in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

Background and aimThe first-line systemic therapy for advanced hepatocellular carcinoma (HCC) involves the use of sorafenib and lenvatinib. The present meta-analysis attempted to compare the therapeutic safety and effectiveness of the two drugs in advanced HCC.MethodsThe library databases of Cochrane, Embase, PubMed, and Web of Science were systematically searched to identify eligible studies comparing the long-term outcomes of sorafenib and lenvatinib use in advanced HCC patients. Overall survival (OS) was considered the primary endpoint, whereas the progression-free survival (PFS), severe adverse events (AEs), objective response rate (ORR), and disease control rate (DCR) were considered the secondary endpoints.ResultsThe present systematic review included 8 nonrandomized studies and 1 randomized controlled trial, comprising a total of 1, 914 cases. OS in patients receiving lenvatinib was better than that in patients receiving sorafenib [hazard ratio (HR): 1.23; 95% confidence interval (CI): 1.04–1.45]. Additionally, patients who received lenvatinib exhibited better PFS, ORR, and DCR (HR: 0.89, 95% CI: 0.79–0.99), [odds ratio (OR: 7.50, 95% CI: 4.43–12.69)], (OR: 7.50, 95% CI: 4.43–12.69), but higher incidences of AEs than those receiving sorafenib (OR: 1.28, 95% CI: 1.08–1.53).ConclusionLenvatinib is superior to sorafenib in treating unresectable HCC patients.     

Drug-eluting bead transarterial chemoembolization followed by apatinib is effective and safe in treating hepatocellular carcinoma patients with BCLC stage C

BackgroundThe present study aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) followed by apatinib in treating hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage C.MethodsTotally, 110 HCC patients with BCLC stage C treated with DEB-TACE followed by apatinib were consecutively enrolled. Treatment response (including complete response rate (CR), objective response rate (ORR) and disease control rate (DCR)), survival data (progression-free survival (PFS), overall survival (OS)), and adverse events were documented during the follow-up.ResultsCR, ORR and DCR were 25.5%, 77.2% and 79.1% at 3 months, then were 29.1%, 59.1% and 71.0% at 6 months, respectively. Regarding survival, median PFS (95%CI) was 6.3 (5.0-7.7) months, meanwhile 1-year and 2-year PFS were 19.8% and 3.3%, respectively; median OS (95%CI) was 16.9 (10.2-23.7) months, then 1-year, 2-year and 3-year OS were 66.5%, 34.7% and 14.2%, respectively. Further subgroup analysis indicated that nodule size, Child-Pugh stage, Eastern Cooperative Oncology Group performance status score and level of portal vein invasion were negatively correlated with PFS or OS, which were further validated by univariate and multivariate Cox's regression analysis. Most adverse events by DEB-TACE and apatinib treatment were mild and well-tolerable.ConclusionDEB-TACE followed by apatinib is effective and safe in treating BCLC stage C HCC patients, indicating its role as an acceptable option in HCC management.     

Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival

Sorafenib has been recommended as first- or second-line treatment for metastatic renal cell carcinoma (mRCC) by several guidelines. The objective of this study is to evaluate the efficacy of sorafenib monotherapy in Chinese patients with mRCC and determine the prognostic clinicopathologic factors associated with survival in these patients.This is a single-arm retrospective study conducted in 2 tertiary medical centers; 140 mRCC patients were enrolled between January 2007 and June 2014. Sorafenib was administered at a dose of 400 mg twice daily, and continued until disease progression, at which point the dose was increased to 600 or 800 mg twice daily, or the onset of an intolerable adverse drug event (ADE) that required dose reduction or temporary suspension of treatment.The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.The median follow-up time was 32 months. The median OS and PFS were 24 months (range, 3–88 months) and 16 months (range, 0–88 months), respectively. Patients with clear cell carcinoma had a greater OS (P = 0.001) whereas sarcomatoid differentiation (P = 0.045) and disease progression (P = 0.010) negatively impacted OS; time from kidney surgery or biopsy to initiation of sorafenib treatment was associated with PFS (P = 0.027). Efficacy analysis revealed that 3 (2.1%) patients achieved complete responses, 28 (20.0%) patients experienced partial responses, 88 (62.9%) patients had stable disease, and 21 (15.0%) patients developed progressive disease. Moreover, the ORR was 22.1%, and the DCR was 85.0%. Most ADEs were classified as grades 1 or 2 with only 14 (10.0%) patients experiencing a severe ADE (grade 3).Sorafenib monotherapy can achieve promising OS and PFS for Chinese patients with mRCC, especially in those with clear cell carcinoma, with manageable adverse events.     

Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients

AIM: To compare the efficacy and safety of chemoem-bolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy(HAIC),including oxaliplatin(OXA),5-fluorouracil(5-FU) and folinic acid(CF),in inoperable hepatocellular carcinoma(HCC) without distant metastasis. METHODS: Eighty-four inoperable HCC patients were enrolled. Thirty-ninepatient sunderwent chemoembolization alone,and the other 45 patients underwent chemoembolization + HAIC(OXA/5-FU/CF) treatment non-randomly. The progression free survival(PFS),objective response rate(ORR),disease control rate(DCR) and adverse reactions were compared between the two groups.RESULTS: A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS(m PFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease,with or without vessel invasion,the chemoembolization + HAIC group showed better m PFS when compared to chemoembolization alone,but no significant difference was found in patients with BCLC stage C disease. The parameter of pain(grade Ⅲ-Ⅳ) in the chemoembolization + HAIC group was increased statistically. CONCLUSION: Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.     

Comparison of DEB-TACE and cTACE for the initial treatment of unresectable hepatocellular carcinoma beyond up-to-seven criteria: A single-center propensity score matching analysis

PurposeTo evaluate clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres and conventional TACE (cTACE) as the initial treatment in patients with unresectable hepatocellular carcinoma (HCC) beyond up-to-seven criteria.MethodsThe study retrospectively assessed the medical records of HCC patients beyond up-to-seven criteria who received the initial treatment of DEB-TACE or cTACE from June 2016 to December 2019 in our institution. To reduce the patient selection bias, propensity score matching (PSM) analysis was used. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. In addition, prognostic factors affecting PFS and OS were analyzed by univariate and multivariate methods.ResultsA total of 312 eligible HCC patients were included in the study, including 140 patients in the DEB-TACE group and 172 patients in the cTACE group. 110 patients were chosen in each group after PSM analysis and there were no significant differences in baseline characteristics (P > 0.05). Before PSM analysis, DEB-TACE had better ORR and DCR compared to cTACE group (P < 0.05). After PSM analysis, the ORR for DEB-TACE group was still higher than that for cTACE group, while no significant difference in the DCR between the two groups. In addition, DEB-TACE group had better survival benefits than cTACE group before PSM analysis (mPFS: 11.5 months vs 9.0 months, P < 0.001; mOS: 24.0 months vs 19.2 months, P = 0.045). Similarly, after PSM analysis, the median PFS and OS in the DEB-TACE group were still higher than that in the cTACE group (mPFS: 11.1 months vs 9.0 months, P = 0.015; mOS: 25.0 months vs 19.0 months, P = 0.030). Further, the univariate and multivariate analysis indicated that DEB-TACE treatment was a positive prognostic factor for PFS and OS.ConclusionDEB-TACE with CalliSpheres microspheres might be an effective and safe treatment for patients with unresectable HCC beyond up-to-seven criteria.     

雷替曲塞联合伊立替康治疗晚期结直肠癌的临床观察

目的分析雷替曲塞联合伊立替康治疗晚期结直肠癌的疗效及安全性。 方法纳入中国医学科学院肿瘤医院内科2015年1月至2018年12月收治的34例既往一线或二线使用含氟尿嘧啶类化疗方案失败的晚期结直肠癌患者,接受雷替曲塞联合伊立替康方案治疗,主要观察终点为客观有效率（ORR）,次要观察终点包括疾病无进展生存时间（PFS）、总生存时间（OS）、疾病控制率（DCR）和安全性。 结果34例患者病理确诊均为结直肠腺癌。近期疗效中观察到部分缓解（PR）为6例,疾病稳定（SD）为25例,疾病进展（PD）为3例,客观有效率（ORR）为17.6%（6/34）,疾病控制率（DCR）为91.2%（31/34）。其中,二线患者ORR为21.7%（5/23）,DCR为91.3%（21/23）;三线患者ORR为9.1%（1/11）,DCR为90.9%（10/11）。34位患者全部追踪至疾病进展,疾病无进展中位生存时间（mPFS）为180天（95% CI：157.2~202.8）,截止2020年2月27日末次随访未观察到中位总生存时间（mOS）,平均OS（389.0±51.1）天。其中,接受二线治疗患者的mPFS为193天,平均OS（412.0±61.5）天。接受三线治疗患者的mPFS为150天,mOS为311天。治疗后肿瘤标志物CEA与CA19-9水平均有降低,其中CA19-9治疗前后平均水平为（169.8±48.0）U/mL和（143.8±57.7）U/mL（t=0.700,P=0.655）。CEA治疗前平均水平为（255.0±40.6）ng/mL,治疗后为（104.2±32.4）ng/mL,下降趋势经比较差异具有统计学意义（t=1.759,P=0.001）。安全性方面,常见不良反应包括恶心呕吐、腹泻、白细胞及中性粒细胞减少、血红蛋白降低和转氨酶升高等,多为Ⅰ~Ⅱ级,Ⅲ级不良反应有中性粒细胞减少（2/34）、白细胞减少（1/34）和转氨酶升高（1/34）,无Ⅳ级不良反应及化疗相关死亡事件发生。 结论雷替曲塞联合伊立替康治疗晚期结直肠癌疗效确切,安全性良好。其中二线治疗ORR与国内外既往研究相似,但不良反应更低,值得临床进一步推广应用。     

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data

Background

The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.

Methods

The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.

Results

From February 2022 to November 2022, 145 patients were enrolled. After a median follow-up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator-assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune-mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non-viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.

Conclusion

The results reported in this first real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial in terms of PFS, ORR and safety.     

Comparative efficacy and safety for second-line treatment with ramucirumab,regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis

Background:The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment.Methods:A systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0.Results:A total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50–0.90).Conclusions:The present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.     

Portal Vein Embolization can Prevent Intrahepatic Metastases to Non-Embolized Liver

Background/Aims: To determine the efficacy of portal vein embolization (PVE) against unresectable hepatocellular carcinoma (HCC). Methodology: We conducted a comparative study using 17 patients with HCC determined to be unresectable and who received a combination of PVE and transarterial chemoembolization (TACE) (PVE group) and 22 HCC patients with tumors in the unilateral lobe, which were treated only with repeated TACE (TACE group) from January 2000 to December 2008. Results: There were no significant differences in background factors except for gender between the two groups. The cumulative intrahepatic recurrence rates in the non-portal-embolized area (in the contralateral lobe for the TACE group) at 1 year and 3 years was 41.1% and 58.8% in the PVE group and 77.3% and 81.8% in the TACE group, respectively. The former was significantly lower (p<0.05). The cumulative overall survival rate at 1 year, 3 and 5 years was 88.2%, 38.2% and 38.2% in the PVE group, and 68.1%, 22.7% and 8.5% in the TACE group, respectively. The former was significantly higher (p<0.05). Conclusions: Although in patients with unresectable HCC, when HCC is localized in the portal-embolized area, PVE combined with TACE can prevent intrahepatic metastasis to the non-portal-embolized area and improve overall survival.