Pembrolizumab Approved for Treating Recurrent or Metastatic Head and Neck Cancer

Clinicians now have a new treatment option for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The US Food and Drug Administration (FDA) is giving the green light to pembrolizumab (Keytruda) at a fixed dose of 200 mg every 3 weeks for HNSCC patients with disease progression on or after platinum-containing chemotherapy.   

The approval for this indication was announced August 8, 2016, and it is based on tumor response rate and durability of response under the FDA’s accelerated approval regulation. Continued approval for this indication will include verification and description of clinical benefit in future confirmatory trials.

“Head and neck cancer is a complex disease that historically has been associated with high recurrence rates and poor long-term outcomes, highlighting the critical need for new treatment options,” said Tanguy Seiwert, MD, associate director of the Head and Neck Cancer Program and assistant professor of medicine at The University of Chicago, in a news release. “The approval of Keytruda for previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma is an important step forward in treating this disease.”

For HNSCC patients, PD-L1 testing is not needed prior to use. Pembrolizumab is already approved for treating unresectable or metastatic melanoma and metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy.

The new approval is based on data from the KEYNOTE-012 study, which included 192 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy and ECOG performance status (PS) of zero or one. The data showed an objective response rate (ORR) of 16%, complete response rate of 5%, with responses of 6 months or longer observed in 82% (n=23 of 28) of the responding patients. ORR and duration of response were similar regardless of human papilloma virus (HPV) status.

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes. The KEYNOTE-012 trial was a multicenter, nonrandomized, open-label, multicohort phase 1b study in which efficacy was evaluated in 174 of 192.

In HNSCC, serious adverse reactions occurred in 45% of patients receiving pembrolizumab. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional, vomiting, pleural effusion, and respiratory failure.