Head and neck cancer and skull base surgeon Nyall London discusses three key immunotherapy clinical trials including KEYNOTE-012, Checkmate 141 and KEYNOTE-048 that have contributed to Food and Drug Administration approval for nivolumab and pembrolizumab, which are PD-1 inhibitors, for recurrent head and neck squamous cell carcinoma.
mm. Hello everyone. My name is Neil London. I'm an assistant professor of otolaryngology at johns Hopkins within the division of rhinology meaning sinuses and skull base surgery as well as the division of head neck cancer surgery. Today I will be discussing a recent presentation I gave at the American Academy of Otolaryngology Annual meeting as part of a panel addressing immunotherapy for head and neck cancer treatment. The goal of cancer immunotherapy is to activate or harness the immune system to fight cancer. One type of immunotherapy that it was a particular focus of our panel is known as immune checkpoint blockade. Immune checkpoints are natural aspects of our immune system that under normal conditions act as brakes to help prevent an excessive immune response. Cancer is able to utilize these natural mechanisms to avoid detection by the immune system. By blocking these checkpoints with immune checkpoint blockade the brakes can be released, allowing the patient's immune system to recognize and destroy the cancer. One of these immune checkpoint mechanisms is programmed death one or P. D. One which is a co receptor found on the surface of immune cells. This receptor interacts with the ligand called program death ligand one or PD L. One which is found on cancer cells Targeting this pathway with immune checkpoint blockade. Has shown exciting results over the past 10 years for multiple tumor types. The purpose of my presentation in the panel at the american Academy of Otolaryngology. Annual meeting was to discuss the current indications for pd one PDO one immunotherapy for recurrent and metastatic head neck squamous cell carcinoma in particular. I discussed three key clinical trials including kino 12 Checkmate 1 41 in kino 48 that have contributed to food and Drug administration approval for novel A mob and symbolism AB, which RPG one inhibitors for recurrent or metastatic head next chromosome carcinoma. To briefly briefly summarized these trials. Both keynote 12 and checkmate 141 included head neck cancer patients that had been previously treated and were refractory to platinum based chemotherapy in standard of care regimens. Both of these trials demonstrated that these agents are generally well tolerated whether response rate between 13-18%. The most exciting results, however, included a long duration of response, which has been a significant improvement over previous therapies. These trials led to the FDA granting approval in 2016 for novel a mob and Embolism Ab for the treatment of patients with recurrent head neck or metastatic squamous cell carcinoma. Refractory to platinum based regimens. The third clinical trial I discussed was keynote 48 which was a multi center randomized phase three trial of untreated locally incurable recurrent or metastatic head neck squamous cell carcinoma patients were randomized into liberalism Avallone embolism ab plus chemotherapy or Cytoxan fabulous chemotherapy. This clinical trial found that embolism ap improved the overall survival in the US where they combined positive PDO one score greater than or equal to one and was associated with substantially longer duration of response in all recurrent or metastatic head neck squamous cell carcinoma patient populations. These results help to support FDA approval in 2019 for pimple is a mob is frontline treatment for recurrent or metastatic head next from cell carcinoma, either in combination with chemotherapy or as a single agent in tumors with a combined positive score greater than or equal to one. Thanks for listening Today, it will be exciting to see future developments and immunotherapy for improving treatment outcomes for our head neck cancer patients. Yeah.