Ezra Cohen, MD
Immunotherapy and novel multikinase inhibitors continue to play an important role for patients with head and neck cancer, particularly as ongoing clinical trials are further exploring these agents.
The field already has 2 immunotherapy approvals with PD-1 agents. Pembrolizumab (Keytruda) was granted an accelerated approval by the FDA in August 2016 for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma following progression on a platinum-based chemotherapy. Then in November 2016, the FDA approved nivolumab (Opdivo), another PD-1 inhibitor, for patients with metastatic or recurrent disease for a similar indication.
“We’ve come to learn that immunotherapy is effective in patients with head and neck cancer,” said Ezra Cohen, MD.
In an interview during the 2017 OncLive®
State of the Science SummitTM
on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer, Cohen, professor of medicine, Division of Hematology/Oncology, associate director for Translational Science, Moores Cancer Center, University of California (UC), San Diego, discussed the role of immunotherapy, the potential of entrectinib, and the importance of multidisciplinary teams for the treatment of patients with head and neck cancer.
OncLive: Can you provide an overview of treatment options for patients with advanced head and neck cancer?
There are [immunotherapy] drugs and single agents for patients with platinum-refractory disease. In my talk, I discussed those data and the reason behind their approvals.
The excitement that is yet to come is around combinations of immunotherapies and the integration of chemotherapy with radiation. Hopefully, that will have the ability to cure more patients.
Can you discuss immunotherapy combinations in head and neck cancer?
When we look at the most exciting combinations in head and neck cancer, it is important to understand what we know about the biology of the disease. For an anti–PD-1 drug to be effective, we know that an immune response has happened.
We have anti–PD-1/PD-L1 agents that are activating T cells, but when those T cells are at the tumor, they still may not be effective because they are suppressed by so many other things in that tumor microenvironment, such as Tregs (regulatory T cells), myeloid derived suppressor cells, macrophages, and fibroblasts.
We are seeing that agents can affect other processes, for instance how STAT3 inhibitors affect myeloid-derived suppressor cells, Tregs, and natural killer cells, and an IDO inhibitor can affect both T cells and partially myeloid-derived suppressor cells. We are seeing a doubling or tripling of response rates, with many of those responses being complete responses. It is still in the early days, but these are very exciting data.
What do you hope community oncologists will take away from this discussion regarding immunotherapy?
The most important thing to take away regarding immunotherapy is that it is now the standard of care for patients with recurrent, metastatic, platinum-refractory disease.
Immunotherapy is moving into the first-line setting very rapidly. We are going to see data from phase III trials in late 2018 into 2019. It would not surprise me if immunotherapy augmented existing chemotherapy. In 2019 or 2020, we are going to begin to look at immunotherapy in the curative setting with the hope that we can cure more patients. The message would be: immunotherapy is here, but look out for more to come in the near future.
Can you discuss the role of entrectinib in head and neck cancer?
Entrectinib is a drug that inhibits kinases at very low molecular level. It’s a specific and potent inhibitor of ROS1
, and NTRK
. We have come to understand that, for some cancers, the NTRK
gene can fuse with other elements—usually transcription factors—and activate the cancer phenotype in multiple ways. That fusion is centrally controlled by the biology of that cancer cell and that tumor. We’ve seen that by inhibiting that, we can often see dramatic responses in patients.
We presented a case of a patient with anaplastic thyroid cancer who had failed multiple lines of therapy, including chemotherapy, radiation, and other types of targeted therapies that are approved for thyroid cancer. We discovered that the tumor had this NTRK3
fusion and, within 10 days, the patient went from being dependent to being out of the hospital.