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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
Open accessAbstract
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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Metadata
- Authors
- Carbognin, L., Pilotto, S., Milella, M., Vaccaro, V., Brunelli, M., Caliò, A., Cuppone, F., Sperduti, I., Giannarelli, D., Chilosi, M., Bronte, V., Scarpa, A., Bria, E., & Tortora, G.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-06-18
- Volume
- 10
- Issue
- 6
- Pages
- e0130142
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W634312238
- Cited by
- 447
- References
- 59
- FWCI
- 29.25
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.1371/journal.pone.0130142
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- Carbognin, L., Pilotto, S., Milella, M., Vaccaro, V., Brunelli, M., Caliò, A., Cuppone, F., Sperduti, I., Giannarelli, D., Chilosi, M., Bronte, V., Scarpa, A., Bria, E., & Tortora, G. (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. PLOS ONE. https://doi.org/10.1371/journal.pone.0130142
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