PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses

Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response, which has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, have now been approved for clinical use.

Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non-small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of approximately 25-40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard-of-care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD-1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD-1 inhibitors are associated with adverse events that have immune etiologies, with grade >3 adverse events typically reported in ≤16% of patients. However, the majority of immune-mediated adverse events (including grade 3-4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD-1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD-1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations. This article is protected by copyright. All rights reserved.

Pharmacotherapy. 2016 Jan 29 [Epub ahead of print]

Patrick J Medina, Val R Adams

Department of Pharmacy: Clinical and Administrative Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA. , Pharmacy Practice and Science Department, University of Kentucky College of Pharmacy, Lexington, KY, USA.