Everett Vokes, MD
As immunotherapy continues to make headway in several different cancer types, these agents are only just arriving to the treatment landscape of head and neck cancer.
Earlier this month, the FDA approved nivolumab (Opdivo) for patients with metastatic or recurrent squamous cell carcinoma of the head and neck following progression on platinum-based therapy. That approval was based on results from the CheckMate-141 study, which demonstrated a median overall survival (OS) benefit with nivolumab when compared with investigator’s choice.
This agent has now joined the ranks of pembrolizumab (Keytruda), which received its FDA approval in August 2016 as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma following progression on a platinum-based chemotherapy, based on objective response rates in the phase Ib KEYNOTE-012 study.
In an interview with OncLive
at the 2016 Chemotherapy Foundation Symposium, Everett Vokes, MD, chair, Department of Medicine, University of Chicago Medicine, and 2013 Giants of Cancer Care winner for Head & Neck Cancer, offered his expert insight on the impact that these emerging immunotherapy agents will have on the treatment of patients with head and neck cancer.
OncLive: Please provide an overview of your talk at the meeting.
: My talk was an overview of where we are in head and neck cancer. Traditionally, we have 2 kinds of settings in head and neck cancer: those with recurrent disease and those that are previously untreated who are treated with curative intent for locoregionally advanced disease. In all of these settings, we have new drugs to consider and we have current treatments to consider.
Let’s start with recurrent disease, and by that, I mean recurrent where it is no longer treatable with salvage surgery or salvage radiation—there are some cases when the tumor comes back and can still be saved for cure. But when that is not an option, or the disease presents with distant metastases, then we look to systemic therapy.
Traditionally, that has been a triple-drug regimen of the so-called EXTREME regimen, with cetuximab (Erbitux) added to a doublet of platinum and 5-FU. Now many people substitute that with a carboplatin regimen or with a taxane, because the toxicity profiles differ, but with that kind of a 3-drug regimen, we get median survival ranges of about 10 months—maybe a little bit longer for those who have HPV-driven tumors, where survival may be longer. And maybe a group in between that is not known to be HPV-driven, but p16-positive; you get into various biomarker differentials there.
That is pretty much the state of the art—a triplet, and then we can follow that with a number of single agents, or sometimes cetuximab is given later, or a drug like gemcitabine is tried, or methotrexate. But it’s overall very unsatisfying.
Like in many other diseases, then, the checkpoint inhibitors come in, and here we now have 2 agents that have been FDA-approved after having been previously IRB-approved for clinical investigations. They are pembrolizumab and nivolumab. Those 2 agents are now available. They are active, and of course, we don’t have direct comparisons, so the trial setup is a little bit different for the 2 of them.
I will start with nivolumab because I think that that is a definitive phase III trial, where patients who had failed a platinum-based regimen within 6 months of initial treatment were then randomized to nivolumab or a standard of care that the investigator could choose from—second-line, in other words—after platinum, and that could be docetaxel, methotrexate, or cetuximab. And in that direct comparison, the checkpoint inhibitor was superior for OS, and it was also superior, but not immediately (there’s a fairly sharp dropoff in curves, but then a separation of curves), for progression-free survival.
It’s the picture we’ve seen in other diseases, that many patients don’t benefit. In fact, probably the majority don’t benefit, but those who do are benefitting enough to lift the entire survival curve to be superior. Furthermore, if a given patient responds, it can be for a long time, certainly much longer than what we’ve observed in chemotherapy-based regimens.
Pembrolizumab is the other drug, and that has not been tested in a phase III trial, but also, extensively, as a single agent in a large phase II trial. It, too, has been approved, and the activity looks very similar to what we would have expected, particularly now knowing how nivolumab faired in comparison. Response rates are around 20%, and sometimes we see very long responses, and what appears to be a group of patients who survive for very long periods of time.
These are the 2 agents, and of course, their toxicity profiles are known. They’ve been described by now, and they are not different in patients with head and neck cancer.