Efficacy and toxicities of adding molecular targeted agents to first-line chemotherapy in the treatment of advanced biliary tract cancer: a systematic review and meta-analysis.
OBJECTIVE
The purpose of this study was to assess the efficacy and toxicities of adding molecular targeted agents (MTAs) to first-line chemotherapy in the treatment of advanced biliary tract cancer (BTC).


METHODS
An extensive search for relevant clinical trials was conducted in electronic databases (PubMed, Web of Science, and Cochrane) and abstracts presented at meetings. Prospective randomized controlled trials (RCTs) reporting the efficacy and toxicity of chemotherapies with or without MTAs in advanced BTC were selected. The endpoints were overall survival (OS), progression-free survival (PFS), and grade 3 or 4 toxicities. The results were expressed as hazard ratio or relative risk (RR), with their corresponding 95% confidence intervals.


RESULTS
The final analysis included a total of 855 advanced BTC patients from six RCTs. Compared with chemotherapy alone, the combination of MTAs with chemotherapy significantly improved overall response rate (ORR) (RR 1.68, 95% confidence interval: 1.28-2.19,P<0.001). And there was also a tendency to improve PFS in the combination regimens (hazard ratio 0.89, 95% confidence interval: 0.78-1.02,P=0.097) but not for OS (hazard ratio 1.01, 95% confidence interval: 0.90-1.13,P=0.93). Subgroup analysis according to targeted agents indicated that the addition of anti-epidermal growth factor receptor agents to chemotherapy significantly improved ORR and PFS, but it did not translate into OS benefits. Additionally, equivalent frequencies of grade 3 or 4 neutropenia, anemia, thrombocytopenia, nausea, and vomiting were found between the two groups excepting for diarrhea.


CONCLUSIONS
The present study indicates that the addition of anti-epidermal growth factor receptor agents to first-line chemotherapy in advanced BTC offers an improved ORR and PFS, but not for OS. Further RCTs with larger samples are warranted to confirm our findings.
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing.
Sheng
S
Zhao
Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People's Republic of China.
Yanping
Y
Miao
Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People's Republic of China.
Ruijun
R
Wang
Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People's Republic of China.
Haidong
H
Guo
Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People's Republic of China.
Feng
F
Jin
Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People's Republic of China.
Xiuling
X
Guo
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing.
Tianyou
T
Luo
biliary tract cancer; meta-analysis; molecular targeted agents; randomized controlled trials