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Immunotherapy in the Peri-Operative Setting of HNSCC

Panelists:Ezra Cohen, MD, FRCPSC, FASCO, UC San Diego; Joshua M. Bauml, MD, University of Pennsylvania; Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center; Barbara A. Burtness, MD, Yale University School of Medicine
Published: Monday, Oct 02, 2017



Transcript: 

Ezra Cohen, MD: Jared, we talked a lot about the idea of curing patients with locally advanced head and neck cancer. Is there a role for immunotherapy in that setting?

Weiss, MD: I hope so. I don’t know yet. So, let’s talk about what we do know. At ASCO, we saw safety data from KEYNOTE-412 that showed us it is safe to combine pembrolizumab with chemoradiotherapy. As for efficacy data, it will be a long time before we have hints of those. I have an ongoing trial with collaborators looking at pembrolizumab alone with radiation therapy, with patients for whom cisplatin is indicated but there are some contraindications, like high frequency, hearing loss, or tinnitus. Others are doing similar work. And I think in the next year, we’re going to get a flurry of safety data on combinations of immunotherapy and radiation that will then empower efficacy design studies to ask, how should we do that? Should it be in combination with platinum and radiation? Should it be a single agent? In which patients?

The other place that I think this can be evaluated in is an adjuvant or neoadjuvant fashion. We have a trial that is to open within a few weeks combining carboplatin/nab-paclitaxel and durvalumab preoperatively for locally advanced patients, with the advantage that, biologically, we’ll be able to capture pre- and posttreatment tissue and do all kinds of comparisons as well, with blood, along the way. And Josh, I know you have a related effort in the adjuvant setting.

Joshua M. Bauml, MD: That’s right. So, working with Tanguy Seiwert at the University of Chicago, we have a multi-site investigator-initiated study that’s looking at patients who are at very high risk for recurrence. We’re taking patients who have N2b, N3 lymphadenopathy and oligometastatic disease—the patients for whom, after chemoradiotherapy, you are saying, “Gosh, there’s at least a 50% chance this person is going to recur”—and those patients are randomized to either immunotherapy with pembrolizumab or placebo for a year.

No one gets excited about including a placebo here, but remember, these patients are generally watched. We don’t give them a therapy, we just sit on our hands and get a little scared. And so, this gives the opportunity to incorporate an immunotherapy earlier. In this minimal residual disease state, considering other immunotherapeutics from the hematologic malignancy world, there’s reason to think that immunotherapy may be more effective when there’s not a huge amount of tumor right there. It’s a really neat niche where we’ll be able to incorporate immunotherapy.

Ezra Cohen, MD: I think we’re certainly going to see a lot more data in patients with locally advanced disease. Jared, you alluded to some neoadjuvant data that were also presented at this year’s ASCO, mostly to look at biomarkers around pembrolizumab responsiveness, but at least with the idea that one could give a dose of pembrolizumab safely and the intriguing thought that it may actually have an effect on the tumor. Of course, that has to play out and the data have to mature. With all of those things in mind, we do now have a few ongoing phase III trials looking at immunotherapy in a context of chemotherapy radiation and also cetuximab radiation.

Transcript Edited for Clarity 

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Transcript: 

Ezra Cohen, MD: Jared, we talked a lot about the idea of curing patients with locally advanced head and neck cancer. Is there a role for immunotherapy in that setting?

Weiss, MD: I hope so. I don’t know yet. So, let’s talk about what we do know. At ASCO, we saw safety data from KEYNOTE-412 that showed us it is safe to combine pembrolizumab with chemoradiotherapy. As for efficacy data, it will be a long time before we have hints of those. I have an ongoing trial with collaborators looking at pembrolizumab alone with radiation therapy, with patients for whom cisplatin is indicated but there are some contraindications, like high frequency, hearing loss, or tinnitus. Others are doing similar work. And I think in the next year, we’re going to get a flurry of safety data on combinations of immunotherapy and radiation that will then empower efficacy design studies to ask, how should we do that? Should it be in combination with platinum and radiation? Should it be a single agent? In which patients?

The other place that I think this can be evaluated in is an adjuvant or neoadjuvant fashion. We have a trial that is to open within a few weeks combining carboplatin/nab-paclitaxel and durvalumab preoperatively for locally advanced patients, with the advantage that, biologically, we’ll be able to capture pre- and posttreatment tissue and do all kinds of comparisons as well, with blood, along the way. And Josh, I know you have a related effort in the adjuvant setting.

Joshua M. Bauml, MD: That’s right. So, working with Tanguy Seiwert at the University of Chicago, we have a multi-site investigator-initiated study that’s looking at patients who are at very high risk for recurrence. We’re taking patients who have N2b, N3 lymphadenopathy and oligometastatic disease—the patients for whom, after chemoradiotherapy, you are saying, “Gosh, there’s at least a 50% chance this person is going to recur”—and those patients are randomized to either immunotherapy with pembrolizumab or placebo for a year.

No one gets excited about including a placebo here, but remember, these patients are generally watched. We don’t give them a therapy, we just sit on our hands and get a little scared. And so, this gives the opportunity to incorporate an immunotherapy earlier. In this minimal residual disease state, considering other immunotherapeutics from the hematologic malignancy world, there’s reason to think that immunotherapy may be more effective when there’s not a huge amount of tumor right there. It’s a really neat niche where we’ll be able to incorporate immunotherapy.

Ezra Cohen, MD: I think we’re certainly going to see a lot more data in patients with locally advanced disease. Jared, you alluded to some neoadjuvant data that were also presented at this year’s ASCO, mostly to look at biomarkers around pembrolizumab responsiveness, but at least with the idea that one could give a dose of pembrolizumab safely and the intriguing thought that it may actually have an effect on the tumor. Of course, that has to play out and the data have to mature. With all of those things in mind, we do now have a few ongoing phase III trials looking at immunotherapy in a context of chemotherapy radiation and also cetuximab radiation.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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