Perioperative Immunotherapy in LA-HNSCC: From Evidence to Clinical Practice

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Dr. Le Tourneau:
Welcome to CE with GLC. I'm Dr. Christophe Le Tourneau. Here with me today is Dr. Marc Oliva. Hi, Marc.

Let's start today's discussion with a brief overview of perioperative immunotherapy in resectable, locally advanced head and neck squamous cell carcinoma. Dr. Oliva, can you tell our audience why perioperative immunotherapy matters?

Dr. Oliva:
For sure, yes. I think that we are currently shifting the paradigm. So the treatment for locally advanced head and neck squamous cell carcinoma, resectable, hasn't changed for the past 2 decades. Currently, till now, the standard of care was surgery followed by radiation or radiation plus chemotherapy based on high-risk features such as extranodal extension or positive margins. And with that, the survival rates of this patient population were—we are looking at 50% to 60% 5-year overall survival rates for this patient population, so definitely quite a range and margin to improve those curative rates.

So definitely, there's a space for immunotherapy in the neoadjuvant or perioperative setting in locally advanced head and neck cancer. So far, the trials looking at the role of immunotherapy in the setting of radiation-based therapy have not been positive, and so there's a lot of hope in the neoadjuvant setting, and there's a strong rationale to sustain that development.

So when we have the tumor in place, the anti-PD-1 therapy is expected to expand the T-cell response, having all the full antigen repertoire in place before resection. But moreover, I think the role of the anti-PD-1 would be to create a memory in order to target potentially microscopic residual disease and distant disease that we are not seeing at diagnosis and also sustain that response over time, therefore leading to durable postoperative immunity that will have the disease control for more and more time.

And the KEYNOTE-689 study actually is evaluating this. This is the first trial that evaluated in a phase 3 randomized study the incorporation of pembrolizumab before surgery and during the adjuvant portion with radiation plus/minus cisplatin, and then maintenance portion up to a year. And it has shown a benefit in event-free survival, and this is the first study actually to show a benefit in event-free survival. This has led to the regulatory approval of this approach and this regimen for patients with locally advanced head and neck cancer that are resectable and that are PD-L1 CPS positive, at least 1 or above.

Now, currently, the challenges are in how to implement this regimen in the clinical practices.

Dr. Le Tourneau:
Yeah, I think what you said is very important. I mean, there is a strong rationale, and what we have seen is that in other cancer types, such as lung cancer or triple-negative breast cancer, this strategy of neoadjuvant immunotherapy has been successful as well. So I guess we're very happy to see a positive trial in the head and neck cancer space.

Well, our time is up, so we hope you found this overview useful. So thanks for listening.

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