Unmet Needs in Recurrent HNSCC

Transcript:Ezra Cohen, MD: Let’s transition now from the standards of therapy that we’ve been talking about: multidisciplinary care, cytotoxic chemotherapy, EGFR inhibition, and some of the emerging data around, especially immunotherapy in head and neck cancer. Let’s first set the stage, Viktor, if you don’t mind. What’s the unmet need for patients with head and neck cancer?

Viktor Grünwald, MD: So, the question will be for what part of the population do we talk about? And I think that has been a theme among this discussion that we have, that we have different populations. And HPV-positive disease has a completely different requirement than HPV-negative tumors. And for HPV-positive, we have a high amount of Asians that do survive. So, long-term survivorship is really already in place for these patients. Whatever we do for localized disease, for definite treatment, it will have those patients live long enough to face their late term toxicity.

So, de-escalation certainly is the goal for these patients. And for those that are HPV-negative, they’re a high amount of tobacco smokers. For those, we have long-term outcomes I’m not satisfied with. It’s not enough for what we deliver here with our treatment. We certainly have to improve. Maybe it is a more intensified treatment approach in these patients, and that’s something Tanguy referred to as well. New induction therapies are the way to go. And I think there are many ways to envision the data. It’s not quite clear, very controversial. How do we approach this?

Ezra Cohen, MD: And so, I’m hearing you say for a group of patients with good prognosis, HPV-positives, you’re thinking about how to reduce the long-term toxicity and maintain cure for a group of patients with a worse prognosis—let’s say HPV-negative—and asking how can we improve cure rates, because we’re not satisfied. Let’s move from the locally advanced setting to the recurrent metastatic. What are the unmet needs there? Viktor Grünwald, MD: I think there that it’s much more prevalent because overall survival is very unsatisfying. But we have evolved from single-agent cisplatin to a modality treatment using 5-FU, cisplatin, EGFR inhibition. And still, we are in the range of 1 year of overall survival. This is really an outlier in terms of our overall cancer perspective, what we see in other diseases. It’s about time to move along with head and neck cancer in the relapsed, the metastatic setting, to improve outcome. So, certainly survival is a key issue that we must succeed with if you would like to improve outcome in these patients.

Ezra Cohen, MD: When you think about it, prior to this year, there was 1 drug approved in head and neck cancer in the last 20 years. I think you’re right. I think we’ve fallen short of the advances that other malignancies have seen. Having said that, Tanguy, what is your approach to treating patients with recurrence in metastatic disease, and focus, if you don’t mind, especially on the platinum-refractory patients?

Tanguy Y. Seiwert, MD: I think when a patient fails curative intent therapy—so the patient has recurrence—or if somebody presents up front with metastatic disease, the treatment goals change. I think if somebody has a localized tumor, we will try to re-resect or to resect the tumor, if feasible. And sometimes, we’ll also try re-irradiation, which I think is, for some patients, feasible but a very toxic approach that only few patients can do.

As soon as that’s no longer an option, then we talk about palliation. And as was mentioned, the life expectancy, on average, is about 1 year. Really, our treatments are not very good. If we have patients who have not been refractory to platinum, we would use the extreme regimen or, at least, double chemotherapy. So, plus/minus cetuximab. Most of the time, that’s a platinum plus 5-FU, and then you can add on the cetuximab. In the United States, a lot of us like to actually replace the 5-FU for the side effects and the inconvenience of the taxane. And there are some data emerging, and I think they’re not unreasonable, but the data actually goes for 5-FU.

In patients who fail within 6 months, so the platinum-refractory patients—and that definition is a little bit arbitrary—but by-and-large, we would say those patients are the ones who should go on to single-modality treatment. So, in the past, up until a few weeks ago, the recommendation in the United States would have been for a taxane, for methotrexate, or for cetuximab, single-agent. However, recently, we saw very exciting data on multiple studies that that patient population may actually have great benefit from immunotherapy, and I think we all were involved in this.

And so, on August the 5th in the United States, we actually saw approval of the first immunotherapy—that being pembrolizumab, a PD-1 inhibitor—for patients who are platinum-refractory. We likely will see approval on a second agent also very soon. But, I think it’s exciting. As you mentioned, for 20 years, we’ve had a single drug approved, that is cetuximab. And a lot of discussion has been had about how effective it is. But now we have an agent that really changes the paradigm, that’s a new class of treatment. And we actually are seeing amazing benefit in a subgroup of patients, where long-term benefit is something that I think we’ve never seen before.

Transcript Edited for Clarity