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

BMC Cancer

Research Article

Luciana Gontijo de Oliveira Clark¹  Otávio Augusto C. Clark¹  Luciano Paladini¹  Tobias Engel Ayer Botrel² 

[1] Evidencias - A Kantar Health Company, Av. José de Souza Campos, 550 - 7°. andar (salas 71 e 72), Nova Campinas, 13092-123, Campinas, São Paulo, Brazil;Evidencias - A Kantar Health Company, Av. José de Souza Campos, 550 - 7°. andar (salas 71 e 72), Nova Campinas, 13092-123, Campinas, São Paulo, Brazil;CIOP - Centro Integrado de Oncologia e Pesquisa, Rua Santo Antônio 200, sala 301, 37701-036, Poços de Caldas, Minas Gerais, Brazil;

关键词: Chemotherapy;    Bevacizumab;    Metastatic colorectal cancer;    Systematic review;    Meta-analysis;   

DOI  :  10.1186/s12885-016-2734-y

 received in 2015-02-02, accepted in 2016-06-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundColorectal 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). MethodsSeveral 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).ResultsThe 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).ConclusionThe 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.

【 授权许可】

CC BY   
© The Author(s). 2016