Insights From: Ezra Cohen, MD, Moores Cancer Center; UC San Diego Health; Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center
Ezra Cohen, MD: We now have 2 approved agents in the United States that are targeting PD-1. They’re both antibodies in recurrent or metastatic squamous cell carcinoma of the head and neck. The first is pembrolizumab, which garnered approval based on nonrandomized data. These are data from an expansion cohort of patients with recurrent metastatic head and neck cancer. Many of those patients were refractory to therapy, including to platinum and cetuximab. Compound that with a second study, called the KEYNOTE-055 trial, that specifically enrolled patients who had been platinum- and cetuximab-refractory, and we now have a dataset of over 150 patients, clearly demonstrating that pembrolizumab is active in these patients. The response rate is in the high teens, with a very promising median overall survival and a 1-year survival somewhere around 40%.
Nivolumab, the second agent to get approved only a few months after the approval of pembrolizumab, was approved on the basis of randomized data. This is the CheckMate-141 study that compared nivolumab to standard of care, single-agent treatment in patients who were platinum-refractory. Platinum refractoriness, in that study, was defined in 2 ways: either patients who were treated with platinum-based therapy in the locally advanced setting and then progressed within 6 months of curative-intent therapy or patients who had had platinum-based therapy in the first-line recurrent metastatic setting and then progressed. Those 2 major cohorts were included, and the comparator was single-agent methotrexate, docetaxel, or cetuximab, according to investigator choice.
What we saw in CheckMate-141 was a doubling of 1-year survival: from about 17% in the control arm to 36% in the nivolumab arm. We saw an increase in response rate. The response rate with nivolumab was about 13%, and, importantly, we saw a much better toxicity profile: 13% grade 3 or grade 4 adverse events with nivolumab compared to about 40% on the single-agent standard therapy, either chemotherapy or cetuximab. And based on those data, nivolumab was approved for patients with recurrent metastatic head and neck cancer who were platinum-refractory.
Jared Weiss, MD: The availability of checkpoint inhibitors has radically changed the landscape of the standard of care treatment for recurrent metastatic head and neck cancer. Previously, the standard of care was a platinum-doublet plus cetuximab followed by a second-line cytotoxic agent. There were 2 major weaknesses to those second-line agents: they didn’t work and they were very toxic. Otherwise, they were great. This is really a revolution in that we have a totally new mechanism of action that is less toxic, that actually works. And it actually works in a way that’s very meaningful to patients’ values.
Patients don’t come into the office saying, “I want this new, better therapy. My hope is that you can add 3.5 weeks to my life, on average.” Patients come in and say, “Please give me a chance at being alive in a year for my daughter’s wedding” or “Please give me a chance of being alive in 2 years to see my first grandchild born” or whatever else it is that’s important to that individual patient. This is the first class of agents, ever, in head and neck cancer that allows us to offer the patients a legitimate chance at that. And we can do it without beating them up in the process.