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

The programmed cell death protein 1 (PD-1) checkpoint is a step in a pathway that prevents the activation of T-cells. Inhibitors of this pathway are designed in order to restore a patient’s antitumor immune response, which becomes suppressed during formation of tumors. Once the T-cells are activated, the immune system starts to attack tumors in the body. Immuno-oncology agents that can restore antitumor immune responses are a new class of medications that have just recently been approved for clinical use. Medications nivolumab and pembrolizumab are two such immuno-oncology agents used to inhibit the PD-1 pathway.

Researchers in this article highlight the response characteristics distinctive to immune checkpoint inhibitors as well as provide pharmacokinetic and pharmacodynamic data for pharmacists and physicians. These researchers have studied these new medications in those with advanced melanoma, metastatic non-small cell lung cancer, and advanced renal cell carcinoma. But although there are many benefits to using these drugs, there have also been many adverse events encountered in those taking this new class of medication. Along with the classic immune-mediated adverse effects expected to be seen when taking anti-cancer drugs, the PD-1 inhibitors also have potential for developing autoreactive T-cells, leading to inflammation across a range of tissues. It is for this reason that patients with a history of autoimmune diseases were excluded from these clinical trials. Despite these adverse reactions, survival rates of the patients taking these medications have increased compared to patients taking standard treatment options.

I feel that although there are many adverse events associated with this new class of cancer drug, and although these drugs were hastened to become approved by the FDA, their efficacy is greatly needed in the management of various cancers. And as demonstrated in the article, if pharmacists collaborate with physicians effectively, the majority of immune-mediated adverse effects can be managed with concurrent use of other medications to ease these symptoms without discontinuation becoming necessary.

Medina, Patrick J., and Val R. Adams. “PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.” Pharmacother. (2016): n. pag. Wiley Online Database. Web. 15 Feb. 2016.