Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

被引:93
作者
Ayer Botrel, Tobias Engel [1 ,2 ]
de Oliveira Clark, Luciana Gontijo [1 ]
Paladini, Luciano [1 ]
Clark, Otavio Augusto C. [1 ]
机构
[1] Evidencias, Av Jose de Souza Campos 550,7 Andar,Salas 71&72, BR-13092123 Campinas, SP, Brazil
[2] CIOP, Rua Santo Antonio 200,Sala 301, BR-37701036 Pocos De Caldas, MG, Brazil
关键词
Chemotherapy; Bevacizumab; Metastatic colorectal cancer; Systematic review; Meta-analysis; ESMO CLINICAL RECOMMENDATIONS; PHASE-III TRIAL; COOPERATIVE-ONCOLOGY-GROUP; PROGRESSION-FREE SURVIVAL; AGITG MAX TRIAL; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; MUTATION STATUS; RECTAL-CANCER;
D O I
10.1186/s12885-016-2734-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). Results: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade = 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). Conclusion: The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.
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页数:19
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