Joshua Bauml, MD
Immunotherapy in head and neck cancer continues to evolve and advance patient care. Challenges remain in the field, however, such as how to better target patients with HPV-associated disease, says Joshua Bauml, MD.
In an interview with OncLive
, Joshua Bauml, MD, assistant professor of Hematology/Oncology and co-deputy director for the Lung/Head and Neck Medical Oncology Clinical Research Program, Abramson Cancer Center, University of Pennsylvania, discussed the current role of immunotherapy in this disease, potential next steps, and unmet needs in HPV-associated head and neck cancer.
OncLive: What is the current role of immunotherapy in head and neck cancer?
Immunotherapy has a key role to play to in the management of head and neck cancer. Patients who have metastatic head and neck cancer currently have very limited options, so the arrival of PD-1 inhibitors has been a huge boon for patients. Specifically, head and neck cancers have overregulation of PD-L1 and PD-L2, which are known to be biomarkers of response to PD-1 inhibition. In addition to that, much of head and neck cancer is virally mediated. Virally mediated tumors tend to have a relatively high mutational burden, which also tends to lead to response to immunotherapy. So, it is complete logical to utilize immunotherapy in the management of head and neck cancer.
This has led to a couple of studies that are worth mentioning. KEYNOTE-012 was the first one—this was a multicohort phase I study looking at pembrolizumab (Keytruda) in the management of recurrent or metastatic head and neck cancer. This was a standard phase I study, so it included anyone with prior treatments, no certain restriction. But what they saw was there was a pretty impressive response rate, much better than what you would expect from standard-of-care agents.
The subsequent study with pembrolizumab was KEYNOTE-055. This study specifically focused on patients who had disease that was refractory to both platinum and cetuximab (Erbitux). This is a particularly [high-need] group because those patients really have no option, the only historical comparator that has been used amongst those patients is methotrexate, which has a response rate of about 5% or lower, with significant toxicity. The PD-1 inhibitors have a lot of benefits there, because it actually has very little toxicity, and significant activity. So, the response rates in KEYNOTE-012 and KEYNOTE-055—which was a specific subgroup of highly ill and highly pretreated patients—were pretty much identical. That was really reassuring that this is a different treatment paradigm.
At the same time we presented KEYNOTE-055, CheckMate-141 was also presented. This was a randomized phase III study that compared nivolumab (Opdivo) to 3 different chemotherapeutic options for patents who platinum-refractory head and neck cancer. The investigators had the choice of giving methotrexate, docetaxel, or cetuximab. That study, in a randomized phase III setting, showed an overall survival benefit for nivolumab versus investigators choice chemotherapy. Based upon KEYNOTE-012, and separately based upon CheckMate-141, both nivolumab and pembrolizumab are both FDA approved for the treatment of head and neck cancer after progression on a platinum.
What are the next steps for immunotherapy in this disease?
I think 1 of the key next steps of immunotherapy is moving it earlier in the course of treatment. As I mentioned, we are currently giving it for metastatic patients who have progressed on platinum, but immunotherapy has significant advantages in the earlier setting as well. Patients who have radiation, for instance, secrete a large amount of their tumor antigens as a result of radiation, and this may act as a sort of automated vaccine to enhance the response to immunotherapy. This is really exciting.
This year at ASCO there were 2 studies presented looking at immunotherapy earlier. One evaluated pembrolizumab along with radiation in locally advanced head and neck cancer. That study was really small, and what we can say is, it seems relatively safe.