MSI-H and dMMR are markers for abnormalities in cancer cells that prevent DNA replication and postreplicative DNA repair.1 These biomarkers are found most commonly in cancers of the endometrium, stomach, and colon. The incidence of MSI-H or dMMR in these tumors appears to be lower in advanced disease than in early-stage disease; about 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.2

FDA approval was based on data from five unpublished, single-arm trials of pembrolizumab (summarized in the package insert) that included a total of 149 previously treated adults with various MSI-H or dMMR metastatic or unresectable tumors (90 patients had colorectal cancer). The overall objective response rate was 39.6% and the complete response rate was 7.4%. The median duration of response had not been reached by the end of the study; 78.0% of patients had a response duration of ≥6 months. Adverse reactions, including immune-mediated effects, were similar to those reported previously with pembrolizumab.

The recommended adult dosage of pembrolizumab for this indication is 200 mg IV (2 mg/kg up to a maximum of 200 mg for children) every 3 weeks for a maximum of 24 months. The cost for one adult dose is about $9162.3

Pembrolizumab was previously approved for treatment of unresectable or metastatic melanoma,4 metastatic non-small cell lung cancer (NSCLC), including nonsquamous NSCLC in combination with pemetrexed and carboplatin,5 recurrent or metastatic head and neck squamous cell carcinoma, refractory classical Hodgkin lymphoma, locally advanced or metastatic urothelial carcinoma,6 and recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.