Ezra Cohen, MD: Just like in all spheres of oncology, we’re beginning to personalize therapy for patients with head and neck cancer—especially for locally advanced head and neck cancer—and taking all of what we know into account. So, tell us about how we’re doing that. What are the data? What efforts are happening in going forward?

Barbara A. Burtness, MD: The data are sparse. We’ve known for a long time that organ preservation can be achieved without sacrificing survival with the use of chemotherapy and cisplatin. And then, with long-term follow-up of the Larynx Intergroup Preservation trial, we began to suspect that there was an increase in noncancer mortality with the use of high-dose cisplatin and radiation. And yet, we have not had anything obvious to substitute in for that. There are good data that cetuximab is a good radiation sensitizer. That may be somewhat different by HPV status, but we are still waiting for compelling results comparing cisplatin/radiation to cetuximab/radiation. I think we need to focus on trying to learn what the causes of the increased noncancer mortality were. I think people suspect that aspiration pneumonia is a part of it, but I think accelerated renal disease and vascular disease are also going to prove to be important in understanding your patient’s underlying health. Doing the best that you can to preserve renal function, I think, is going to be important.

With the HPV-positive patients, we’re talking about a group of patients with a median age probably a little bit under 60, a very low comorbidity burden—some of them are lifetime non-smokers—and a highly curable cancer. The idea that we’re giving them a therapy that, in some way, may compromise their ability to live a full life despite curing their cancer I think has motivated a lot of the most innovative work in this field of locally advanced disease. And so, we have a lot. Patients will find a lot of options in going on clinical trials that attempt to achieve the same cure rates that we’ve been seeing in the historic trials of cisplatin and radiation. But take into account the things that Jared was saying: it’s important how your larynx works, it’s important how your swallowing is, it’s important whether or not you have chronic pain, and it’s important whether or not your other health remains good and we aren’t compromising your survival.

Ezra Cohen, MD: In fact, we now have prospective data that we can dramatically reduce the dose of radiation in some patients with HPV-positive disease.

Barbara A. Burtness, MD: Yes. So, there are 2 trials that did the calculations that the long-term toxicity was more related to radiation than to chemotherapy, and they used this 54-gray breakpoint for the pharyngeal constrictor dose that Jared mentioned. And so, the first was from ECOG E1308. Patients got a 3-drug chemotherapy regimen, not untoxic in and of itself. They got 3 cycles of that, and then they were categorized as clinically complete responders or clinically incomplete responders. The incomplete responders went on to full-dose radiation and cetuximab and the patients who had had a complete response had their radiation capped at 54 gray, again given with cetuximab. Those data were published in the JCO this past December, demonstrating that—for patients who did not have bulky cancers, non-T4s, and who did not have a significant smoking history—with 54 gray, you could attain 2-year survival of 96%. And in fact, the low-dose radiation patients in that trial did better than the full-dose radiation patients.

There has been another study from UCLA taking a similar approach of non-cetuximab chemoradiation, but again, for responders, capping at 54 gray and again showing greater than 90% survival. So, that is one paradigm. Another paradigm is trying to get rid of the cisplatin. Another paradigm is using minimally invasive surgery. I think all of these competing ideas have value. I think the first step is going to be to compare them to historical approaches, and then the second step is going to be figuring out who is the patient who is best served by getting rid of chemotherapy. Who is the patient who might still has a risk for metastatic risk and is best served by reducing the dose of radiation?

Transcript Edited for Clarity