Efficacy and safety of anti PD-1/PD-L1 in the treatment of advanced non-small-cell lung cancer: a single arm meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

FENG Haiming ¹ , ZHAO Ye ² , LI Min ³ , LIN Junping ² , ZHANG Jianhua ⁴ , MA Jianxing ¹ , JING Tao ¹ ,  WANG Cheng ¹ ,  LI Bin ¹ , JIANG Peng ¹

1. Department of Thoracic Surgery, the Second Hospital of Lanzhou University, Lanzhou, 730000, P.R.China;
2. The Evidence-Based Medicine Center of Lanzhou University, Lanzhou, 730000, P.R.China;
3. Department of Intensive Medicine, the Second Hospital of Lanzhou University, Lanzhou, 730000, P.R.China;
4. Department of Thoracic Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, 518100, P.R.China;

Corresponding author：

WANG Cheng, Email: wangc88@sina.com; LI Bin, Email: dr.ebin@outlook.com

Keywords：

Non-small cell lung cancer; Monoclonal antibodies; PD-1; PD-L1; Monoclonal antibody; Meta-analysis

DOI：

10.7507/1672-2531.201705025

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ObjectivesTo systematically review the efficacy and safety of anti-PD-1/PD-L1 antibody in the treatment of advanced non-small cell lung cancer (NSCLC).MethodsNon-comparative binary data on anti-PD-1/PD-L1 monoclonal antibodies in the treatment of advanced NSCLC from PubMed, EMbase and The Cochrane Library databases were collected from inception to August 1^st 2017. Two reviewers screened literature, extracted data and independently evaluated the risk of bias of included studies, then meta-analysis was conducted by RevMan 5.3 software.ResultsForty-four trials were included. The results of meta-analysis showed that the pooled objective response rate (ORR), overall 1-year survival rate (OSR_{1 year}) and progression-free survival rate at 1 year (PFSR_{1 year} ) of anti-PD-1/PD-1 antibodies were 22% (RD=0.22, 95%CI 0.20 to 0.25, P<0.001), 54% (RD=0.54, 95%CI 0.46 to 0.63,P<0.001) and 27% (RD=0.27, 95%CI 0.20 to 0.33,P<0.001), respectively. The rate of adverse effects (AEs) was 61% (RD=0.61, 95%CI 0.54 to 0.68,P<0.001), and the rate of grade 3 to 5 AEs was 13% (RD=0.13, 95%CI 0.10 to 0.15,P<0.001).ConclusionsAnti- PD-1/PD-1 antibodies show good efficacy and safety in the treatment of advanced NSCLC. Due to limited quality and quantity of included studies, more high-quality studies are needed to verify the above conclusions.

Citation： FENG Haiming, ZHAO Ye, LI Min, LIN Junping, ZHANG Jianhua, MA Jianxing, JING Tao, WANG Cheng, LI Bin, JIANG Peng. Efficacy and safety of anti PD-1/PD-L1 in the treatment of advanced non-small-cell lung cancer: a single arm meta-analysis. Chinese Journal of Evidence-Based Medicine, 2018, 18(3): 322-333. doi: 10.7507/1672-2531.201705025 Copy

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2. Santarpia M, Giovannetti E, Rolfo C, et al. Recent developments in the use of immunotherapy in non-small cell lung cancer. Expert Rev Respir Med, 2016, 10(7): 781-798.
3. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin, 2016, 66(4): 271-289.
4. JKobayashi K, Hagiwara K. Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsm all cell lung cancer (NSCLC). Target Oncol, 2013, 8(1): 27-33.
5. Cufer T, O'Brien MER, Ovcaricek T. Systemic therapy of advanced non-small cell lung cancer: major-developments of the last 5-years. Eur J Cancer, 2013, 49(6): 1216.
6. Mahesh KPO, Alagar M, Jothibasu S. Role of immunotherapy in the treatment of advanced non-small-cell lung cancer. Future Oncol, 2014, 10(1): 79-90.
7. Zimmerman MP, Mehr SR. Targeted programmed cell death in lung cancer treatment. Am J Manag Care, 2014, 20(5): SP155-157.
8. Wolchok JD. PD-1 Blockers. Cell, 2015, 162(5): 937.
9. Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol, 2013, 31(5): 616-622.
10. Zatloukal P, Heo DS, Park K, et al. Randomized phase II clinical trial comparing tremelimumab with best supportive care following first-line platinum-based therapy in patients with advanced non-small cell lung cancer. J Clin Oncol, 2009(15 Suppl): 8071.
11. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol, 2015, 33(17): 1974-1982.
12. Caroline R, Antoni R, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet, 2014, 384(9948): 1109.
13. Weber JS, D'Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol, 2015, 16(4): 375-384.
14. Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 5. 2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2017, 15(4): 504.
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16. Gettinger S, Horn L, Antonia SJ, et al. Clinical activity and safety of anti-programmed death-1(PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (PTS) with advanced non-small cell lung cancer (NSCLC). Ann Oncol, 2012, 23(9 Suppl): 405-406.
17. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 2012, 366(26): 2443-2454.
18. Brahmer JR, Horn L, Antonia SJ, et al. Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. J Thorac Oncol, 2013, 8: S365-S366.
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24. Balmanoukian AS, Rizvi NA, Garon EB, et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC): novel therapies/experimental therapies. Int J Radlat Oncol, 2014, 90(5): S1-S2.
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26. Garon EB, Leighl NB, Rizvi NA, et al. Safety and clinical activity of MK-3475 in previously treated patients (pts) with non-small cell lung cancer (NSCLC). J Clin Oncol, 2014, 32(15 Suppl): 8020.
27. Gettinger SN, Shepherd FA, Antonia SJ, et al. First-line nivolumab (anti-PD-1, BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status. J Clin Oncol, 2014, 32(15 Suppl): 8024.
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29. Ramalingam SS, Mazières J, Planchard D, et al. Phase II study of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced, refractory squamous non-small cell lung cancer: metastatic non-small cell lung cancer. Int J Radlat Oncol, 2014, 90(5): 1266-1267.
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Chinese Journal of Evidence-Based Medicine

Efficacy and safety of anti PD-1/PD-L1 in the treatment of advanced non-small-cell lung cancer: a single arm meta-analysis

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