April is head and neck cancer month. According to the American Association for Cancer Research (AACR), alcohol and tobacco use are major risk factors for developing head and neck cancers. However, infection with the cancer-causing types of the human papillomavirus (HPV) also increases the risk for certain forms of the cancer, as well as eating preserved or salted foods, poor oral hygiene, occupational exposure to wood dust, asbestos, and synthetic fibers, radiation exposure, and Epstein-Barr virus infection in endemic regions, including southeast Asia.
Head and neck cancers are more common among men than women. Additionally, most patients who are diagnosed with this type of cancer are 50 years or older. Symptoms include a lump or sore on that does not go away or heal, difficulty swallowing, changes in voice, or a sore throat that does not resolve or heal.
Trials such as the KEYNOTE-048 study (NCT02358031), which investigated the use of pembrolizumab (Keytruda) as a first line treatment for recurrent or metastatic squamous cell cancer of the head and neck, have changed how head and neck cancers are treated. While many patients recover, many are still affected by life-long disabilities as the result of their disease and treatment.
Stuart J. Wong, MD, a medical oncologist, professor, and director of the Center for Disease Prevention Research at the Medical College of Wisconsin, discussed the KEYNOTE-048 trial, advances in head and neck cancers, and current unmet needs in this patient population in an interview with Targeted Oncology.
TARGETED ONCOLOGY: Can you discuss the evolution of treatments for patients with head and neck cancer?
WONG: Probably the biggest evolution is the integration of immune oncology into our treatment of head and neck cancer. We now have a first line indication for the use of an immune checkpoint inhibitor for patients with recurrent/metastatic head and neck cancer. This has been very successful in improving the overall survival for this patient population. Based upon the success of these agents in the recurrent and metastatic setting, there have been many new studies launched to test immune oncology agents into earlier stages of disease and to test novel immunotherapy combinations. The results of many of those studies are still anxiously being awaited.
TARGETED ONCOLOGY: What are your preferred first-line and later-line treatments in this setting?
WONG: My preferred first line is off of a clinical trial, pembrolizumab. The results of the KEYNOTE-048 study are very exciting and a huge help for patients, however we're still not satisfied with that. My first choice, if at all possible, is to enroll patients in a clinical trial. Roughly about 20% of the patients with recurrent metastatic disease may have long-term survival with the use of pembrolizumab. Other patients receive benefits that may improve their survival, which is fantastic, but we're not satisfied with those results and want to have higher response rates and more patients who would benefit from this therapy and more patients that have long-term survival. The only way we can do this is enroll patients in clinical trials and push the envelope even further and find strategies to improve the outcome of our patients.
TARGETED ONCOLOGY: What are some clinical trials of therapies in this setting right now, including for PD-L1 inhibitors and EGFR inhibitors?
WONG: The most exciting area of research are studies for patients who have progressed on an immune checkpoint inhibitor or have shown initial refractory disease. The most intriguing studies out there are for cellular therapies or other immune strategies. These novel therapies alone or in combination with an immune checkpoint inhibitor may overcome that initial resistance or subsequent resistance. There are many different strategies that are being explored. We are anxiously awaiting their results. As of yet, none of these strategies have proven to be successful compared with standard strategies. But I think in the next few years, we're going to have some really dramatic results; something that will improve the outcome of this population of patients.
TARGETED ONCOLOGY: Can you talk about the role of low dose radiation for these patients?
WONG: This is an exciting area of research. The idea is that many of our patients with HPV-associated cancer have a favorable outcome and that you might be able to decrease the intensity of therapy and improve their outcome is a very promising strategy. A group from Memorial Sloan Kettering Cancer Center has led an interesting pilot study in which they decrease the intensity of the radiation using a significantly lower dose but kept cisplatin in the treatment regimen. Those results are very promising. The subsequent study of this paradigm and a larger multicenter trial would potentially warrant a sea of change in the way we manage patients. There are other strategies that are attempting to do the same thing. But this is an exciting area of research and something that patients seem to be very interested in exploring. We look forward to clinical trials that employ this technique.
TARGETED ONCOLOGY: Please go into detail on some of the unmet needs that are still relevant in the space.
WONG: The biggest one, I think, is that in clinical research, we still have a small minority of patients with head and neck cancer who enroll in clinical trials. There are many causes for this, but we cannot make progress in the treatment of these cancers unless we have more opportunities for patients to go on clinical trials and more clinical trials to offer to patients. It is frustrating that our progress is slow and that we cannot offer more advances to patients. There are some diseases where a much higher percentage of patients are treated on clinical trials initially and then when they recur, clinical trials are really part and parcel of the standard management of certain diseases. We don't have that luxury in head and neck cancer, and this is something that we need to overcome. There is a desire for patients and for their physicians to make quicker progress. We cannot do that unless we have more resources at our fingertips to allow that to happen, and to make more progress on our patients.
I think the other big area that is in need of progress is supportive care oncology. Many of the treatment modalities that we utilize to cure or attempt to cure our patients have significant morbidity. The adverse effects linger with patients, sometimes for the rest of their life. While we're happy that our patients are able to have their lives extended, or in some cases be cured, it makes us very frustrated that they do so at the expense of, sometimes, lifelong disabilities. We need more research into supportive care and survivorship issues. Many of us are very dedicated to this. But again, that runs into the issue that we have limited resources; there's not as much funding for this kind of research. This is, I would say, a very big unmet need and frequently doesn't rise to the top of discussion when we talk about cancer therapy and clinical trials.
TARGETED ONCOLOGY: Are there any specific upcoming trials or therapies that you think show promise in head and neck cancer?
WONG: If you would ask me in 2 months, I might have some really good ideas for you. I always look forward to our upcoming American Society of Clinical Oncology Annual Meeting. I'm sure this one promises to show some really exciting results. I guarantee in the next few years, we're going to be making some exciting progress with respect to new technologies, especially cellular therapy strategies and immune oncology strategies. I can't put bets on one line of research as being the most promising but there are many exciting lines of evidence that are being explored in ongoing clinical trials and clinical trials that are on the drawing board. I simply would say stay tuned and hopefully we'll have some exciting news in the near future.
