Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors or chemotherapy alone in advanced NSCLC: a meta-analysis of randomized controlled trials.
BACKGROUND
Most patients with advanced non-small-cell lung cancer (NSCLC) require systemic chemotherapy. Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors (TKI; e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, axitinib) has recently been evaluated in patients with NSCLC. However, the advantage of this therapy over chemotherapy alone in patients with advanced NSCLC remains largely unknown.


METHODS
A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and toxicity of chemotherapy plus multitargeted antiangiogenic TKI with chemotherapy alone in patients with advanced NSCLC. PubMed, the ASCO and ESMO databases, and the Cochrane Library were searched for references to published articles. Two reviewers independently assessed the quality of the trials. Data were extracted, and overall response rate (ORR), pooled progression-free survival (PFS), overall survival (OS) with 95 % confidence intervals (CI), and major toxicities/adverse effects were analyzed.


RESULTS
Six RCTs involving 3,337 patients with advanced NSCLC were ultimately analyzed. Compared to chemotherapy alone, chemotherapy plus multitargeted antiangiogenic TKI significantly increased the ORR [relative risk (RR) 1.71, 95 % CI  1.43-2.05] and PFS [hazard ratio (HR)  0.83, 95 % CI 0.76-0.90], but not OS (HR 0.93, 95 % CI 0.83-1.03). Patients who received chemotherapy plus multitargeted antiangiogenic TKI exhibited more rash, diarrhea and hypertension (OR 2.78, 95 % CI  2.37-3.26; OR 1.92, 95 % CI 1.65-2.24; OR  2.90, 95 % CI 2.19-3.84, respectively) and less nausea and vomiting (OR 0.71, 95 % CI 0.60-0.83; OR 0.75, 95 % CI 0.61-0.92, respectively). The incidence of hemorrhage, fatigue, cough, constipation, anorexia, and alopecia were comparable between the two groups.


CONCLUSIONS
Therapy consisting of chemotherapy plus multitargeted antiangiogenic TKI was found to have specific advantages over chemotherapy alone in terms of PFS and ORR. The toxicity was comparable between the two therapies. Therefore, chemotherapy plus multitargeted antiangiogenic TKI may be a safe and valid therapeutic option for patients with advanced NSCLC.
Department of Respiratory and Critical care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, China.
Yong-Ying
YY
Xiao
Ping
P
Zhan
Dong-Mei
DM
Yuan
Hong-Bing
HB
Liu
Tang-Feng
TF
Lv
Yong
Y
Song
Yi
Y
Shi
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases