Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.
The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China ; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Pu-Yun
PY
OuYang
Zhen
Z
Su
Yan-Ping
YP
Mao
Wuguo
W
Deng
Fang-Yun
FY
Xie
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors