[HTML][HTML] Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity …

L Carbognin, S Pilotto, M Milella, V Vaccaro, M Brunelli… - PloS one, 2015 - journals.plos.org
L Carbognin, S Pilotto, M Milella, V Vaccaro, M Brunelli, A Caliò, F Cuppone, I Sperduti
PloS one, 2015journals.plos.org
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 …
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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