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Review
. 2015 Aug:23:32-8.
doi: 10.1016/j.coph.2015.05.011. Epub 2015 Jun 2.

PD-1/PD-L1 inhibitors

Joel Sunshine  1 , Janis M Taube  2
Affiliations
Review

PD-1/PD-L1 inhibitors

Joel Sunshine et al. Curr Opin Pharmacol. 2015 Aug.

Abstract

Tumors may adopt normal physiologic checkpoints for immunomodulation leading to an imbalance between tumor growth and host surveillance. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. Nivolumab and pembrolizumab are the anti-PD-1 antibodies that are currently the furthest in clinical development, and anti-PD-L1 agents under investigation include MPDL3280A, MEDI4736, and BMS-936559. These agents have been used to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma, amongst other tumor types. In this article, we review the updated response results for early clinical trials, note recent FDA actions regarding this class of agents, and summarize results across trials looking at PD-L1 status as a predictor of response to anti-PD-1/PD-L1.

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Figures

Figure 1
Figure 1. Association of PD-L1 expression in pre-treatment tumor specimens with objective response to anti-PD-1/PD-L1 therapy
Numerous studies in multiple tumor types have demonstrated the constant finding that PD-L1 expression enriches for response to anti-PD-1/PD-L1. The weighted average of the ORR across reported studies for patients whose tumors were tested for PD-L1 is 29% (blue dotted line), and if the specimen is PD-L1 (+), this increases to 48% (red dotted line). A significant proportion of PD-L1(−) patients also respond (green line). (Ref. from left to right 10, 40, 41, 35, 18, 17, 22, 32, 42, 43, 44, 33, 21, 25, 45, 16, 16).
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