Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis.
BACKGROUND
Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy.


METHODS
Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed.


RESULTS
In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18).


CONCLUSIONS
Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Minghan
M
Jia
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Weijiao
W
Feng
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Shiyang
S
Kang
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Yaxiong
Y
Zhang
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jianfei
J
Shen
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jiaxi
J
He
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Long
L
Jiang
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Wei
W
Wang
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Zhihua
Z
Guo
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Guilin
G
Peng
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Gang
G
Chen
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jianxing
J
He
1 Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; 2 Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510120, China ; 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Wenhua
W
Liang
Anti-programmed cell death-1 (anti-PD-1); anti-programmed cell death-ligand 1 (anti-PD-L1); non-small cell lung cancer (NSCLC)