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New Therapies for 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 Online: Friday, Sep 08, 2017



Transcript:

Ezra Cohen, MD: I want to touch upon 2 more things that came out of this year’s ASCO meeting. The first is the use of bevacizumab. Barbara, if you could talk about that a little bit.

Barbara A. Burtness, MD: This was an older study. It had been written in 2005, and it was for first-line treatment in metastatic recurrent disease, a platinum-based doublet. This was investigator’s choice—so it could be cisplatin or carboplatin—and a second drug could be 5-FU or docetaxel, and then patients were randomized to receive that with or without bevacizumab. Obviously, during the years that that trial was accruing, cetuximab came on the market and it was not used in either of the frontline arms of this trial, but we think there was a lot of crossover. We were very concerned because bevacizumab had been associated with bleeding in the non–small cell lung cancer trials, and here we had a squamous cancer that could be close to vessels in the mediastinum.

So, there were some exclusion criteria to try to minimize the risk of bleeding. Patients could not go on if they were getting full-dose anticoagulation, if they had a history of hemoptysis leading up to going on the trial, or if there was radiographic evidence the tumor was frankly invading a vessel in the neck. Those seemed to be actually good criteria because in the control arm, the patients who didn’t get bevacizumab, the rate of fatal bleeding was 0%, and you don’t usually get that in a 400-patient study in head and neck cancer. And it was not all that high, actually, in the bevacizumab arm.

What we found from the trial was that bevacizumab significantly increased the response rate to chemotherapy. It significantly increased the progression-free survival, and it nonsignificantly increased the overall survival. The control arm had one of the better overall survivals in this setting ever reported, at 11 months. We attribute that partly to a higher prevalence of HPV than some of the older trials and, then again, to the crossover use of cetuximab, maybe implying that whether or not you give cetuximab as part of the frontline regimen—as it was done in the EXTREME trial, where you include it in a sequence of therapies—doesn’t make a whole lot of difference.

And so, I think of these data in the context where we know that cetuximab improves response rate, but also improves survival. With a lot of exciting new trials coming to look at immuno-oncology agents in the frontline, this trial will not establish a role for bevacizumab in metastatic recurrent disease. But I think there is enough of a signal there to begin to explore combinations, either with immunotherapy or with other targeted agents and either for frontline or salvage use. And you have experience with erlotinib.

Ezra Cohen, MD: I really agree with you, Barbara. I think what the study told us is that bevacizumab is doing something biologically in these patients, something positive, and it is worthwhile exploring. We did a study, now that is a bit dated in terms of the time, combining bevacizumab with erlotinib and saw an encouraging response rate and encouraging progression-free and overall survival. Of course, this was a nonrandomized trial, but the idea of now taking the data that we have with bevacizumab, the criteria for patient selecting, and moving it forward into newer combinations with upcoming newer agents makes a lot of sense to me. Before we completely leave targeted therapies, Jared, what about EGFR tyrosine kinase inhibitors? Is there a role for them anymore in head and neck cancer? And what are some of the data coming out?

Jared Weiss, MD: Interesting question to ask the North Carolina guy. So, there are 2 challenges cetuximab offers that I think these agents might try to address. One is the risk of anaphylaxis, which in my neighborhood is north of 20%, although there are other ways to address that, such as the alpha-Gal assay. These agents don’t have that problem. And the other advantage is that they’re oral. It de-medicalizes the life of our patient. We speak all the time about, in addition to duration of life, wanting to buy our patients quality of life while not coming into the infusion room.

We have 2 relevant data sets, that are large, to talk about. We have a randomized study of afatinib that shows its efficacy in the second-line. While I don’t think there’s an approval yet for it, it does add it to our armamentarium. I’ve used it now and again, and it doesn’t seem to be a problem. And then, more recently, there was a trial combining erlotinib with cytotoxic therapy that again seems to show benefit. And so, I think these aren’t necessarily an improvement over cetuximab. That direct comparison does not exist. There’s no suggestion of superiority in the cross-trial comparison that we’re not allowed to make, but make regularly, but these are additional options available to us—erlotinib with chemotherapy or afatinib on its own.

Transcript Edited for Clarity 

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Transcript:

Ezra Cohen, MD: I want to touch upon 2 more things that came out of this year’s ASCO meeting. The first is the use of bevacizumab. Barbara, if you could talk about that a little bit.

Barbara A. Burtness, MD: This was an older study. It had been written in 2005, and it was for first-line treatment in metastatic recurrent disease, a platinum-based doublet. This was investigator’s choice—so it could be cisplatin or carboplatin—and a second drug could be 5-FU or docetaxel, and then patients were randomized to receive that with or without bevacizumab. Obviously, during the years that that trial was accruing, cetuximab came on the market and it was not used in either of the frontline arms of this trial, but we think there was a lot of crossover. We were very concerned because bevacizumab had been associated with bleeding in the non–small cell lung cancer trials, and here we had a squamous cancer that could be close to vessels in the mediastinum.

So, there were some exclusion criteria to try to minimize the risk of bleeding. Patients could not go on if they were getting full-dose anticoagulation, if they had a history of hemoptysis leading up to going on the trial, or if there was radiographic evidence the tumor was frankly invading a vessel in the neck. Those seemed to be actually good criteria because in the control arm, the patients who didn’t get bevacizumab, the rate of fatal bleeding was 0%, and you don’t usually get that in a 400-patient study in head and neck cancer. And it was not all that high, actually, in the bevacizumab arm.

What we found from the trial was that bevacizumab significantly increased the response rate to chemotherapy. It significantly increased the progression-free survival, and it nonsignificantly increased the overall survival. The control arm had one of the better overall survivals in this setting ever reported, at 11 months. We attribute that partly to a higher prevalence of HPV than some of the older trials and, then again, to the crossover use of cetuximab, maybe implying that whether or not you give cetuximab as part of the frontline regimen—as it was done in the EXTREME trial, where you include it in a sequence of therapies—doesn’t make a whole lot of difference.

And so, I think of these data in the context where we know that cetuximab improves response rate, but also improves survival. With a lot of exciting new trials coming to look at immuno-oncology agents in the frontline, this trial will not establish a role for bevacizumab in metastatic recurrent disease. But I think there is enough of a signal there to begin to explore combinations, either with immunotherapy or with other targeted agents and either for frontline or salvage use. And you have experience with erlotinib.

Ezra Cohen, MD: I really agree with you, Barbara. I think what the study told us is that bevacizumab is doing something biologically in these patients, something positive, and it is worthwhile exploring. We did a study, now that is a bit dated in terms of the time, combining bevacizumab with erlotinib and saw an encouraging response rate and encouraging progression-free and overall survival. Of course, this was a nonrandomized trial, but the idea of now taking the data that we have with bevacizumab, the criteria for patient selecting, and moving it forward into newer combinations with upcoming newer agents makes a lot of sense to me. Before we completely leave targeted therapies, Jared, what about EGFR tyrosine kinase inhibitors? Is there a role for them anymore in head and neck cancer? And what are some of the data coming out?

Jared Weiss, MD: Interesting question to ask the North Carolina guy. So, there are 2 challenges cetuximab offers that I think these agents might try to address. One is the risk of anaphylaxis, which in my neighborhood is north of 20%, although there are other ways to address that, such as the alpha-Gal assay. These agents don’t have that problem. And the other advantage is that they’re oral. It de-medicalizes the life of our patient. We speak all the time about, in addition to duration of life, wanting to buy our patients quality of life while not coming into the infusion room.

We have 2 relevant data sets, that are large, to talk about. We have a randomized study of afatinib that shows its efficacy in the second-line. While I don’t think there’s an approval yet for it, it does add it to our armamentarium. I’ve used it now and again, and it doesn’t seem to be a problem. And then, more recently, there was a trial combining erlotinib with cytotoxic therapy that again seems to show benefit. And so, I think these aren’t necessarily an improvement over cetuximab. That direct comparison does not exist. There’s no suggestion of superiority in the cross-trial comparison that we’re not allowed to make, but make regularly, but these are additional options available to us—erlotinib with chemotherapy or afatinib on its own.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
Community Practice Connections™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations Across Lung, Head and Neck, and Bladder CancersApr 28, 20182.0
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