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Emerging PD-L1 Inhibitors for HNSCC

Insights From: Ezra Cohen, MD, UC San Diego Moores Cancer Center; Robert L. Ferris, MD, PhD, University of Pittsburgh Cancer Institute; Nabil F Saba, MD, FACP, Emory University
Published Online: Wednesday, Mar 08, 2017



Transcript:

Nabil F. Saba, MD:
Some of the checkpoint inhibitors we’re talking about have been used in different tumor types and approved, such as atezolizumab, and there seems to be encouraging activities in bladder cancer. I think the future of atezolizumab in head and neck cancer will probably rely on combination therapies, given the fact that we already have 2 FDA-approved checkpoint inhibitors in the recurrent metastatic setting. So, I think the future is open for combinations with other agents. And certainly, it’s open also for looking at this agent in the definitive therapy setting.

As far as the durvalumab trials, we are still waiting on the results of the PD-L1–negative durvalumab in combination with a CTLA4 inhibitor in patients with a recurrent metastatic disease. We will also be expecting the results of the combination—the same combination in comparison with the extreme regimen—or single-agent durvalumab in the first-line recurrent metastatic disease. There’s also interest in combining durvalumab with vaccines for treatment specifically of HPD–positive-related cancer.

As far as avelumab, there is interest in combination with tumor vaccines, but we are also waiting for the results of the phase III randomized trial combining it with platinum and radiation versus the standard platinum and radiation. So, that would be an interesting trial to look for.

An adjuvant checkpoint inhibitor or adjuvant immune therapy is a question that is very much of interest and is currently under investigation in head and neck cancer. There are a couple of Cooperative Group trials that are examining this question. And the question there is, are these agents helpful in a pure maintenance setting? What is the appropriate way of administering these agents in that setting? Is it in combination with radiation to begin with, which we would give them in maintenance, or is it in a pure maintenance setting where we would basically complete the definitive therapy and afterwards start a pure maintenance with these agents? We still don’t know the clear answer to these questions. But certainly, this is a question that makes sense to explore.

Robert L. Ferris, MD, PhD: Other immunotherapeutic strategies include vaccines. Prevention vaccines against HPV are likely to benefit patients decades down the road. There are also therapeutic HPV vaccines, which might be promising and beneficial to combine with immune checkpoint receptors. There are oncolytic viruses, one of which is FDA-approved for melanoma, and these are now being integrated with immune checkpoints in head and neck cancer. Intralesional injection of T-VEC or other oncolytic viruses, plus immune checkpoint receptors and combinations of HPV vaccines or other vaccines, show that a whole spectrum of immunotherapies, besides the immune checkpoint receptors, open up a new world of treatment for this challenging disease.

Nabil F. Saba, MD: I think, as a general principle, patients should be considered for clinical trials first because clinical trials are really looking to push the envelope compared to the current standard. So, if we hand a clinical trial that is adding something to nivolumab, we will certainly consider putting that patient on the clinical trial as a first option. The KIR inhibitor with nivolumab is very interesting, at least the early data seems to be very encouraging, and it would be a trial we would be enthusiastic in trying to put patients on. Outside of a clinical trial, nivolumab would be the current standard that we would use.

Transcript Edited for Clarity
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Transcript:

Nabil F. Saba, MD:
Some of the checkpoint inhibitors we’re talking about have been used in different tumor types and approved, such as atezolizumab, and there seems to be encouraging activities in bladder cancer. I think the future of atezolizumab in head and neck cancer will probably rely on combination therapies, given the fact that we already have 2 FDA-approved checkpoint inhibitors in the recurrent metastatic setting. So, I think the future is open for combinations with other agents. And certainly, it’s open also for looking at this agent in the definitive therapy setting.

As far as the durvalumab trials, we are still waiting on the results of the PD-L1–negative durvalumab in combination with a CTLA4 inhibitor in patients with a recurrent metastatic disease. We will also be expecting the results of the combination—the same combination in comparison with the extreme regimen—or single-agent durvalumab in the first-line recurrent metastatic disease. There’s also interest in combining durvalumab with vaccines for treatment specifically of HPD–positive-related cancer.

As far as avelumab, there is interest in combination with tumor vaccines, but we are also waiting for the results of the phase III randomized trial combining it with platinum and radiation versus the standard platinum and radiation. So, that would be an interesting trial to look for.

An adjuvant checkpoint inhibitor or adjuvant immune therapy is a question that is very much of interest and is currently under investigation in head and neck cancer. There are a couple of Cooperative Group trials that are examining this question. And the question there is, are these agents helpful in a pure maintenance setting? What is the appropriate way of administering these agents in that setting? Is it in combination with radiation to begin with, which we would give them in maintenance, or is it in a pure maintenance setting where we would basically complete the definitive therapy and afterwards start a pure maintenance with these agents? We still don’t know the clear answer to these questions. But certainly, this is a question that makes sense to explore.

Robert L. Ferris, MD, PhD: Other immunotherapeutic strategies include vaccines. Prevention vaccines against HPV are likely to benefit patients decades down the road. There are also therapeutic HPV vaccines, which might be promising and beneficial to combine with immune checkpoint receptors. There are oncolytic viruses, one of which is FDA-approved for melanoma, and these are now being integrated with immune checkpoints in head and neck cancer. Intralesional injection of T-VEC or other oncolytic viruses, plus immune checkpoint receptors and combinations of HPV vaccines or other vaccines, show that a whole spectrum of immunotherapies, besides the immune checkpoint receptors, open up a new world of treatment for this challenging disease.

Nabil F. Saba, MD: I think, as a general principle, patients should be considered for clinical trials first because clinical trials are really looking to push the envelope compared to the current standard. So, if we hand a clinical trial that is adding something to nivolumab, we will certainly consider putting that patient on the clinical trial as a first option. The KIR inhibitor with nivolumab is very interesting, at least the early data seems to be very encouraging, and it would be a trial we would be enthusiastic in trying to put patients on. Outside of a clinical trial, nivolumab would be the current standard that we would use.

Transcript Edited for Clarity
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Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
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