The FDA has approved pembrolizumab (Keytruda, Merck) as monotherapy in patients whose tumors express PD-L1 (combined positive score [CPS] ≥1), or in combination with platinum and fluorouracil (FU) chemotherapy, as first-line treatment of patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
The approval is based on results from the pivotal phase 3 KEYNOTE-048 trial, which involved 882 patients with metastatic HNSCC who had no prior systemic therapy and were considered incurable by local therapies. Pembrolizumab demonstrated a significant improvement in overall survival (OS) compared with the EXTREME regimen (cetuximab with carboplatin or cisplatin + FU), as monotherapy in patients whose tumors expressed PD-L1 and in combination with chemotherapy in the total study population.
The new indications make pembrolizumab the first anti-PD-1 therapy approved in the first-line setting as monotherapy in patients whose tumors express PD-L1 (CPS ≥1) or in combination with chemotherapy regardless of PD-L1 expression for patients with metastatic or unresectable, recurrent HNSCC. It is also the first anti-PD-1 therapy to demonstrate a statistically significant improvement in OS in these patients.
Immune-mediated adverse reactions, which may be severe or fatal, include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT).
Source: Seeking Alpha, June 11, 2019