Tanguy Seiwert, MD
The treatment landscape of head and neck cancer has changed significantly over the past year. With the approval of pembrolizumab (Keytruda) in August 2016 and nivolumab (Opdivo) in November 2016, immunotherapy has become a key player in patient care.
Following in the tracks of KEYNOTE-012, which led to the approval of pembrolizumab, and CheckMate-141, which led to the approval of nivolumab, several trials are examining whether anti–PD-1/PD-L1 agents can succeed in the frontline, as well as whether combination regimens can build on the single-agent success.
KEYNOTE-048 (NCT02358031), a phase III randomized study, is evaluating the safety and efficacy of pembrolizumab as a first-line treatment alone or in combination with chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma.
Another trial that is currently ongoing is KESTREL (NCT02551159), which is looking at the anti–PD-L1 agent durvalumab, in the first-line setting, as well. This is a phase III randomized, open-label, multicenter, global study of durvalumab alone or in combination with the CTLA-4 inhibitor tremelimumab versus standard of care for patients with recurrent or metastatic head and neck squamous cell cancer who have not received prior treatment.
“There is so much ongoing. The field has really shifted from an area where there was not much going on to now where there is almost too much going on,” said Tanguy Seiwert, MD.
In an interview with OncLive
, Seiwert, assistant professor of medicine, The University of Chicago Medicine, discussed advances and next steps with immunotherapy, as well as the overall challenges and goals for treating patients with head and neck cancer.
OncLive: What is the current role of immunotherapy in head and neck cancer?
: The role of immunotherapy has changed dramatically. In 2016, there was the approval of two anti–PD-1 agents and a lot of interesting and exciting data. For the last 20 or 30 years, there has been very little progress for recurrent metastatic head and neck cancer. The only approval was cetuximab (Erbitux), which actually is not very active. But then, data with immunotherapy came out and it became clear that these drugs have really striking activity—especially when you look at overall survival. We saw data with pembrolizumab, and we saw data with nivolumab, then there was durvalumab, all of which seem to have a striking effect on survival, in particular. At 1 year, about 40% of patients are alive, which is much better than what we typically see. So, it feels like, for the first time, there is really progress because of these novel agents.
Are any of these agents distinguishing themselves?
They are all quite excellent and well tolerated. Whether there are any differences between the agents, that is hard to tell. It seems like they are more similar though, and obviously, we do not have comparisons to look at. It seems like they have certain key features that are shared. There is some debate over slight differences—the dosing can be slightly different and one targets a receptor, one targets a ligand, but by and large, they are more similar than not.
What ongoing research are you excited about?
We have approval of 2 agents in the second-line setting, but we will likely in 2017 or early 2018 see data in the first-line setting. There are 2 trials that will mature, KEYNOTE-048 with pembrolizumab and the KESTREL study with durvalumab.
There are also efforts ongoing in the curative setting. We actually do cure a lot of people with head and neck cancer, but the question is can we introduce or integrate immunotherapy into the curative setting? These studies are starting now.
We actually already saw some combination data from the PD-1 inhibitor nivolumab with lirilumab, an anti-KIR antibody, and that looked quite good. There seems to be excitement about combinations. There will be data about combinations with CTLA-4 inhibitors: durvalumab in combination with tremelimumab, as well as nivolumab with ipilimumab (Yervoy). There is also combination data emerging with other agents, such as talimogene laherparepvec (T-VEC; Imlygic), which is an oncolytic virus, and the IDO1 inhibitor epacadostat.