Which treatment is preferred for advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor in second-line therapy? A meta-analysis comparing immune checkpoint inhibitor, tyrosine kinase inhibitor and chemotherapy

Di Wu, Chongyang Duan, Fenfang Wu, Liyong Chen and Size Chen _

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Oncotarget. 2017; 8:66491-66503. https://doi.org/10.18632/oncotarget.20281

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Di Wu1,*, Chongyang Duan2,*, Fenfang Wu1, Liyong Chen3 and Size Chen1

1 Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China

2 Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China

3 Guangdong Province Key Laboratory for Medical Molecular Diagnostics, China-America Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China

* These authors have equally contributed to this work

Correspondence to:

Size Chen, email:

Liyong Chen, email:

Keywords: immune checkpoint inhibitor, tyrosine kinase inhibitor, chemotherapy, wild-type epidermal growth factor receptor, lung cancer

Received: April 15, 2017 Accepted: July 26, 2017 Published: August 16, 2017


Background: The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy.

Patients and methods: Randomized trials investigating two of the three treatments were searched and included. Multiple treatments comparison and pairwise comparison were performed to assess overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs). The effect of prespecified study-level characteristics was assessed by subgroup analysis and meta-regression.

Results: 12 randomized trials accruing 3341 advanced patients with WT EGFR tumors were analyzed. PD-1/PD-L1 antibody was associated with significantly longer OS and PFS than chemotherapy (OS: HR 0.67, 95% CrI 0.60–0.75; PFS: HR 0.83, 95% CrI 0.73–0.95) and TKI (OS: HR 0.59, 95% CrI 0.50–0.70; PFS: HR 0.75, 95% CrI 0.66–0.84) , while chemotherapy was associated with significantly longer OS (HR 0.88, 95% CrI 0.77–0.99) and PFS (HR 0.75, 95% CrI 0.66–0.84) than TKI.

Conclusions: For advanced NSCLC patients with WT-EGFR tumors in second- or third-line therapy, PD-1/PD-L1 antibody appeared to be the most efficacious treatment, which was followed by chemotherapy. EGFR-TKI was worse than chemotherapy.

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