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Meta-Analysis
. 2015 Jun 18;10(6):e0130142.
doi: 10.1371/journal.pone.0130142. eCollection 2015.

Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

Luisa Carbognin  1 , Sara Pilotto  1 , Michele Milella  2 , Vanja Vaccaro  2 , Matteo Brunelli  3 , Anna Caliò  3 , Federica Cuppone  4 , Isabella Sperduti  5 , Diana Giannarelli  5 , Marco Chilosi  3 , Vincenzo Bronte  3 , Aldo Scarpa  6 , Emilio Bria  1 , Giampaolo Tortora  1
Affiliations
Meta-Analysis

Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

Luisa Carbognin et al. PLoS One. .

Abstract

Background: The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research.

Methods: Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI). Interaction test according to tumor PD-L1 was accomplished. A sensitivity analysis according to adopted drug, tumor type, PD-L1 cut-off and treatment line was performed.

Results: Twenty trials (1,475 patients) were identified. A significant interaction (p<0.0001) according to tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% (95% CI 27.6-41.3%) in the PD-L1 positive and 19.9% (95% CI 15.4-25.3%) in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivolumab and pembrolizumab, with an absolute difference of 16.4% and 19.5%, respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLC, respectively, with no significant difference for genitourinary cancer.

Conclusion: Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Outline of the search—Flow chart of the studies included in the analysis.
Pts: patients; n: number; PD-L1: programmed death-ligand-1; IHC: immunohistochemistry; ORR: overall response rate; NSCLC: non-small cell lung cancer.
Fig 2
Fig 2. Results of the event rate analysis.
ORR: overall response rate; CI: confidence interval; PD-L1: programmed death-ligand-1.
Fig 3
Fig 3. Results of the sensitivity analysis—Overall response rate, with 95% confidence interval in square brackets, according to adopted drug.
Chi2: Chi-square test; PD-L1: programmed death-ligand-1.
Fig 4
Fig 4. Results of the sensitivity analysis—Overall response rate, with 95% confidence interval in square brackets, according to tumor type.
Chi2: Chi-square test; PD-L1: programmed death-ligand-1; NSCLC: non-small cell lung cancer.
Fig 5
Fig 5. Results of the sensitivity analysis.
Panel [A]: overall response rate, with 95% confidence interval in square brackets, according to PD-L1 expression cut-off; Panel [B]: overall response rate with 95% confidence interval in square brackets, according to treatment line. Chi2: Chi-square test; PD-L1: programmed death-ligand-1.
See this image and copyright information in PMC

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