Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis.
Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis.
复制标题
索拉非尼联合经动脉化疗栓塞治疗肝细胞癌的最佳时机：荟萃分析
DOI：
10.1016/j.tranon.2021.101238
复制
发表时间：
2021-12
影响因子：
5
通讯作者：
Zheng R
中科院分区：
文献类型：
--
作者：
Dai Y;Jiang H;Jiang H;Zhao S;Zeng X;Sun R;Zheng R
索拉非尼联合肝动脉化疗栓塞术可延长肝癌患者的生存期。与TACE +安慰剂/单药相比，TACE联合索拉非尼治疗肝癌的疗效和安全性显著提高。索拉非尼联合TACE的时机可能在生存率和不良事件方面存在统计学差异。经肝动脉化疗栓塞术（TACE）联合索拉非尼治疗中晚期肝癌（HCC）是有效的治疗方法之一。虽然联合治疗能有效延长晚期肝癌患者的生存期，但其疗效和安全性仍存在争议，临床价值尚未确定。本荟萃分析旨在评价联合治疗的有效性和安全性，并讨论联合治疗的最佳时机，以获得更好的临床获益。对PubMed、EMBASE、科克伦图书馆、MEDLINE和Web of Science进行了系统综述，以检索2021年5月15日之前发表的相关研究。纳入比较TACE +索拉非尼与TACE +安慰剂/单药治疗的疗效和安全性的研究。两名评审员独立提取研究结果。使用Review Manager（版本5）通过固定/随机效应荟萃分析模型分析数据。3)软件7项随机对照试验（RCT）纳入了1464例不可切除HCC患者（TACE +索拉非尼组734例，TACE +安慰剂或单独治疗组730例）。荟萃分析显示，TACE +索拉非尼组的客观缓解率（ORR）和疾病控制率（DCR）略有改善（ORR：风险比= 1.24; 95%置信区间：1.08-1.42; P = 0.002; DCR：风险比= 1.09; 95%置信区间：1.01-1.18; P = 0.02）。联合治疗明显改善了疾病进展时间（TTP）（风险比：0.73; 95%置信区间：0.55-0.96; P = 0.03）和无进展生存期（PFS）（风险比0.62; 95%置信区间：0.52-0.73，P < 0.00001），但不是总生存期（OS）（风险比：0.93; 95%置信区间：0.59-1.46; P = 0.75）或至不可治疗进展时间（TTUP）（风险比：0.76; 95%置信区间：0.31-1.89; P = 0.56）。此外，联合组不良反应（AE）发生率高于TACE +安慰剂/单药组。亚组分析显示TTP的异质性显著降低（TACE前：P = 0.12，I2 = 48%; TACE后：P = 0.58，I2 = 0%），风险比为0.59（95%可信区间：0.51-0.68; P < 0.00001），表明TACE前联合用药可显著延长TTP，而TACE后联合用药无显著性差异（风险比：0.88; 95%置信区间：0.62-1.24; P = 0.46）。对不良事件敏感性分析显示，TACE前亚组手足皮肤反应、腹泻、皮疹/脱屑、高血压的危险比分别为7.41、2.58、2.14、1.55，TACE后亚组分别为11.34、3.26、3.61、4.11（均P < 0.05）。TACE联合索拉非尼可显著改善TTP和PFS，降低不可切除HCC的不良反应风险水平，尤其是TACE前联合索拉非尼。
Sorafenib in combination with TACE can prolong survival in patients with hepatocellular carcinoma. Compared with TACE + placebo / alone, the combination of TACE and sorafenib can significantly improve the efficacy and safety of hepatocellular carcinoma. The timing of sorafenib combined with TACE may be a statistical difference in terms of survival and adverse events. The combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits. PubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software. 7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I2 = 48%; post-TACE: P = 0.58, I2 = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05). The combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.
登录
查看更多内容
影响因子：
7.6
作者：
Cabrera R;Pannu DS;Caridi J;Firpi RJ;Soldevila-Pico C;Morelli G;Clark V;Suman A;George TJ Jr;Nelson DR
通讯作者：
Nelson DR
经动脉化疗栓塞联合索拉非尼治疗不可切除的肝细胞癌：系统评价和荟萃分析
影响因子：
2.4
作者：
Li L;Zhao W;Wang M;Hu J;Wang E;Zhao Y;Liu L
通讯作者：
Liu L
影响因子：
25.7
作者：
Lencioni, Riccardo;Llovet, Josep M.;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
2.8
作者：
Rizzo, Alessandro;Ricci, Angela Dalia;Brandi, Giovanni
通讯作者：
Brandi, Giovanni
影响因子：
5.8
作者：
Sansonno, Domenico;Lauletta, Gianfranco;Dammacco, Franco
通讯作者：
Dammacco, Franco