Immunotherapy in the Treatment of Cancer: PD-1 Inhibitors

A promising type of immunotherapy involves the inhibition of certain immune checkpoints such as programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). These checkpoint inhibitors work by taking the “brakes” off of the immune system. Opdivo and Keytruda are both PD-1 inhibitors, and Yervoy is a CTLA-4 inhibitor. These are the only currently available checkpoint inhibitors, although numerous therapies are being studied, including antibodies for the PD-1 ligand (PD-L1).

Opdivo and Keytruda are indicated as second-line treatment for metastatic cancers. Both products were released in the past year and have generated tremendous excitement in the oncology community with a potential to change current treatment paradigms.

In the treatment of melanoma, the National Comprehensive Cancer Network (NCCN) states that the PD-1 inhibitors Opdivo and Keytruda are less toxic and have higher response rates than Yervoy, the current standard of care.¹ Opdivo gained a second indication for squamous Non-Small Cell Lung Cancer (NSCLC) in early 2015. The FDA has granted priority review for Keytruda in the treatment of Non-Small Cell Lung Cancer with a decision expected by October 2, 2015, and also priority review for an Opdivo + Yervoy combination in patients with previously untreated, advanced melanoma. A decision by the FDA is expected by September 30, 2015, for use in the treatment of advanced melanoma.

Both Opdivo and Keytruda are being studied in numerous cancer types as monotherapy or combination therapy, and as first- or second-line options. While they represent a promising new class of oncology therapies, their optimal place in therapy continues to evolve, including: length of treatment, sequence in therapy, potential combination therapy, and whether or not the PD-L1 ligand may be used as a predictive biomarker for PD-1 inhibitor activity.

With the potential for use in numerous cancer types and a cost of almost $180,000 per year, the currently available PD-1 inhibitors may have a significant impact on healthcare expenditure. MedImpact continuously monitors existing and new market entrants to ensure appropriate management. As with the PD-1 inhibitors, this includes forecasting the drug pipeline, ongoing clinical review, and a proactive management structure that ensures optimal patient and payor outcomes. Opdivo and Keytruda were reviewed during MedImpact’s second quarter Pharmacy & Therapeutics Committee Meeting, and the drugs will be managed through prior authorization criteria supported by FDA approved labeling and clinical practice guidelines.

Source:
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma Guidelines. Version 3. 2015. http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf.