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Oncotarget. 2016 Nov 8;7(45):73068-73079. doi: 10.18632/oncotarget.12230.

The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis.

Author information

1
Biotherapy Center, Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
2
Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
3
School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
4
Department of Urology, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Japan.
5
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
6
Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
7
Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States.
8
Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science (307 Hospital, PLA), Beijing, China.
9
Molecular and Immunological/Bio-therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing China.
10
Biotherapy Center, Cancer Center, Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong, China.
11
Henan Key Laboratory for Tumor Immunology and Biotherapy, Henan, China.
12
School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.

Abstract

PURPOSE:

To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer.

RESULTS:

Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53-2.41, P < 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22-29.75, P = 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46-3.40, P < 0.001), reduced death risk (HR= 0.53; 95% CI: 0.48-0.57; P < 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30-0.80, P = 0.004) compared with other therapies.

EXPERIMENTAL DESIGN:

Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published before January 31th 2016 were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate.

CONCLUSIONS:

Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers.

KEYWORDS:

PD-1; PD-L1; advanced or refractory cancer; immunotherapy; meta-analysis

PMID:
27683031
PMCID:
PMC5341964
DOI:
10.18632/oncotarget.12230
[Indexed for MEDLINE]
Free PMC Article

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