Efficacy of PD-1/PD-L1 inhibitors against pretreated advanced cancer: a systematic review and meta-analysis

Hao Hu _, Qian Zhu, Xian Shi Luo, Xiong Wen Yang, Hai Dong Wang and Chang Ying Guo

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Oncotarget. 2018; 9:11846-11857. https://doi.org/10.18632/oncotarget.24163

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Hao Hu1,*, Qian Zhu2,*, Xian Shi Luo3,*, Xiong Wen Yang4, Hai Dong Wang3 and Chang Ying Guo5

1Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang, China

2Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China

3Department of General Surgery, Medical College of Nanchang University, Nanchang, China

4Department of Lung Cancer Center, First People's Hospital Chenzhou, Chenzhou, China

5Department of Thoracic Surgery, Jiangxi Province Tumor Hospital, Nanchang, China

*These authors contributed equally to this work

Correspondence to:

Chang Ying Guo, email: [email protected]

Keywords: programmed cell death 1; programmed cell death-ligand 1; overall survival; progression-free survival; meta-analysis

Received: July 07, 2017     Accepted: December 04, 2017     Published: January 11, 2018


Background: Programmed cell death 1 (PD-1) and programmed cell death-ligand 1(PD-L1) inhibitors have captured our attention as new therapeutic options for several tumor types. Nonetheless, the differences in efficacy between PD-1/PD-L1 inhibitors and conventional treatments (chemotherapy or targeted therapy) in pretreated advanced cancer patients remain unclear.

Materials and Methods: A systematic literature search was conducted to identify phase III randomized controlled trials (RCTs)-based investigations of PD-1(nivolumab, pembrolizumab)/PD-L1 inhibitors (atezolizumab) against pretreated advanced cancer. We evaluated these trials for inclusion, assessed each study's risk of bias and selected relevant data for analysis.

Results: The eligibility criteria were met by 5,093 patients from 8 phase III RCTs. PD-1/PD-L1 inhibitors significantly extended overall survival relative to the conventional treatment, expressed as hazard ratio [HR] (0.72, 95% CI, 0.66 to 0.77, P < 0.001) and median month difference (2.83 months, 95% CI, 1.87 to 3.78, P < 0.001). The progression-free survival HRs favored PD-1/PD-L1 inhibitors over conventional treatment (0.88; 95% CI, 0.82 to 0.95, P = 0.002), whereas median month difference was just the opposite (-0.69 months, 95% CI, -1.14 to -0.24, P < 0.001).

Conclusions: Among selected patients with pretreated advanced cancer, PD-1/PD-L1 inhibitors, compared with conventional treatments (chemotherapy or targeted therapy), were associated with improvement in overall survival (2.83 months) but not progression-free survival. These findings will be important in considering PD-1/PD-L1 inhibitors in the treatment of pretreated advanced cancer and have implications for future study design.

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