Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

Zhuansun, Yongxun; Huang, Fengting; Du, Yumo; Lin, Lin; Chen, Rui; Li, Jianguo

doi:10.21037/jtd.2017.03.104

Cited by 15 publications

(10 citation statements)

References 20 publications

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“…Programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have proved to play a predominant role in cancer immune surveillance [ 4 , 5 ]. In solid tumors, PD-1/PD-L1 blockade has achieved profound progress, showing vast potential for tumor therapy [ 6 – 9 ]. In order to improve survival outcome of patients with sarcoma, the association between PD-L1 expression and prognosis of sarcoma patients has been examined, but the results have been controversial.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis

et al. 2017

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BackgroundThe prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma.Materials and MethodsA comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes.ResultsFourteen eligible studies comprising 868 patients were selected for analysis. Pooled hazard ratios indicated that the association of PD-L1 expression with overall survival in bone sarcoma (osteosarcoma and chondrosarcoma) patients was statistically significant (1.987, 95% CI: 1.224–3.224, p = 0.005), as was its association with event-free survival in bone and soft-tissue sarcoma patients (3.868, 95% CI: 2.298–6.511, p = 0.000). Additionally, the expression of PD-L1 was positively correlated with the infiltration of programmed death 1 (PD-1) positive T-lymphocytes (OR: 4.012, 95% CI: 2.391–6.733, p = 0.000).ConclusionsOur meta-analysis indicated that high PD-L1 expression is likely to be a negative factor for patients with sarcomas and that it predicts worse survival outcomes.

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Section: Introductionmentioning

confidence: 99%

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis

et al. 2017

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“…It worth noting that the ORR of PD-1/L1 combination therapy with chemotherapy or EGFR-TKIs in the second or more line setting decreased compared with that in the first line setting. This might be partly associated with the reason that monotherapy of PD-1/L1 inhibitors achieved lower efficacy in the second or more line setting for NSCLC patients 46…”

Section: Discussionmentioning

confidence: 99%

<p>A pooled meta-analysis of PD-1/L1 inhibitors incorporation therapy for advanced non-small cell lung cancer</p>

Wan

et al. 2019

OTT

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Objective: Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in non-small cell lung cancer (NSCLC) patients. Incorporation of anti-PD-1/L1 antibodies into other therapeutic regimens (including CTLA-4 inhibitors, chemotherapy, EGFR-TKIs and IDO inhibitors) is currently in active clinical research. This meta-analysis summarized recent developments in four combination regimens of PD-1/L1 inhibitors. Methods: We searched PubMed, the Cochrane Library and the Embase database up to July 2018, on the combination therapy of PD-1/L1 inhibitors in NSCLC patients. Results: Seventeen trials were finally included in the current meta-analysis. The combined objective response rate s (ORR) for PD-1/L1 inhibitors in combination with CTLA-4 inhibitors, chemotherapy, EGFR-TKIs, and IDO inhibitors were 32% (19%–44%), 49% (46%–53%), 55% (28%–83%) and 35% (20%–50%) respectively. The combined ORR for first line PD-1/L1 inhibitors combination with CTLA-4 inhibitors, chemotherapy, and EGFR-TKIs were 35% (17%–53%), 51% (46%–56%) and 43% (−7%–93%) respectively, and the combined ORR in the second or more line setting were 36% (8%–65%), 17% (−13%–46%), 39% (19%–59%) and 35% (20%–50%) respectively. The pooled 6-month progression-free survival rate (6m PFSr) and 1-year overall survival rate (1y OSr) for combination therapy of PD-1/L1 inhibitors with CTLA-4 inhibitors or chemotherapy were 35% or 65% (6m PFSr) and 31% or 70% (1y OSr) respectively. Anti-PD-1/L1 drugs combined with anti-CTLA-4 drugs exhibited a more potent efficacy on PD-L1 positive patients (OR=0.33, 95%CI: 0.12–0.88). This trend was not observed in patients receiving combination therapy of PD-1/L1 inhibitors with chemotherapy (OR=0.96, 95%CI: 0.51–1.78). Conclusion: The included four combination regimens were potential treatment strategies and well tolerated for NSCLC patients. Further, the therapy lines and PD-L1 expression status were correlated with treatment efficacy.

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“…Two meta-analyses have tried to explore the efficacy of PD-1/PD-L1 inhibitors. One meta-analysis included only 3 trials of PD-1/PD-L1 inhibitors [ 57 ] and the other included only 4 trials [ 58 ]. Furthermore, these studies included 1 small phase II trials among them, and only NSCLCs patients were included.…”

Section: Discussionmentioning

confidence: 99%

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

Zhu

Luo

et al. 2018

Oncotarget

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BackgroundProgrammed 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 MethodsA 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.ResultsThe 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).ConclusionsAmong 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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Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

Cited by 15 publications

References 20 publications

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis

<p>A pooled meta-analysis of PD-1/L1 inhibitors incorporation therapy for advanced non-small cell lung cancer</p>

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

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