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Current Perspectives on HPV+ Head and Neck Cancer
Dr. Shah: Welcome to PracticeUpdate. I'm your host, Dr. Aman Shah, and I'm delighted to be here with PracticeUpdate advisor and head and neck specialist, Dr. Barbara Burtness. Welcome, Dr. Burtness.
Dr. Burtness: Thank you very much.
Dr. Shah: So, there is this recent study, HN002, that seems to have very important implications, practical implications on how you treat HPV-positive head and neck cancer. Could you give us a little background as to why the study was conducted and what the issues are?
Dr. Burtness: HN002 is a very interesting study. I think it'll take some time for us to realize whether or not we're going to adjust practice on the basis of this study alone, but the study arose because we became concerned that patients who had favorable-risk HPV-associated oropharynx cancer were being over-treated with our current paradigm of 70 Gy of radiation, 3 doses of high-dose cisplatin. Prior studies even incorporated induction chemotherapy, and as we became aware that the cure rate for radiation and cisplatin in patients who have HPV-associated disease is very high, in the high 80s or low 90s, we wondered whether or not these patients could be cured with treatment that was a little bit less intensive or didn't cause quite as much morbidity, and so the ideas that we've had about how you might do that, one is to use systemic therapy to shrink the disease, so that you could radically reduce the dose of radiation.
Another that's currently moving forward in studies is to look at immunotherapy, and a third was to ask the question of whether or not chemotherapy could be omitted altogether because these are such radiosensitive cancers, and the concern there was that we know that some of these patients develop distant metastases. Would it turn out that the small amount of chemo that we give during radiation had been contributing to control of distant metastases?
So, HN002 was a randomized phase 2 trial, and it's been reported now with 2 years of follow-up. So, it may be with HPV-related disease where metastases can sometimes present late. It may still be a little bit early to interpret this, but what they found was reducing radiation in both arms from 70 Gy to 60 Gy and in one arm giving that together with weekly cisplatin, very important to say the weekly cisplatin was still full dose at 40 mg/m2 per week, and in the other arm 60 Gy of radiation without any chemotherapy.
Patients who were eligible had to fit the favorable-risk criteria. They were all nonsmokers or very light, remote smokers, and the results, as presented by Sue Yom at ASTRO earlier this month, showed that both groups did extremely well. The radiation plus chemotherapy dose-intensified approach did meet their prior hypothesis. So, the control at 2 years was over 90%. Even though the difference wasn't so large between the two arms, at 87% for the radiation alone, that actually did not meet their statistical hypothesis.
So, I think that future studies that look at chemo/radiation will feel more comfortable using the weekly schedule of 40 40 mg/m2 per week rather than the 100. We know that causes less kidney toxicity, less ototoxicity, it's easier on the patients; and I think looking at that 60-Gy dose as a de-intensification dose moving forward looks very reasonable in the wake of this study.
Dr. Shah: Very interesting. So, for a community oncologist who is seeing a favorable-risk HPV-positive patient, it seems like she should do the 60-Gy of radiation. No? Okay.
Dr. Burtness: I think that the follow-up is a little too short to draw that conclusion at this point.
Dr. Shah: Okay. Okay. So, you would not apply this? Okay.
Dr. Burtness: And we saw the publication earlier this year of the legacy RTOG trial 1016, which was a very large trial of full-dose radiation with cisplatin versus full-dose radiation with cetuximab and it took a long time for the difference between the arms to emerge, but platinum remained superior in that study. So, I think the bottom line is 70 Gy with 100 per meter squared of cisplatin times 3, or times 2 if you use altered fractionation, is the standard of care.
Dr. Shah: Okay.
Dr. Burtness: If you have a patient who has good reasons to be ineligible for 100 of cisplatin but who is eligible for 40 of cisplatin, and that would be the ototoxicity, the renal risk factors, the borderline renal function, I do think HN002 helps you to feel quite good about using weekly cisplatin.
Dr. Shah: Okay. So, you would also stay with the cisplatin? You would not suggest that you change to cetuximab or something which is a little bit less toxic?
Dr. Burtness: No. I think the RTOG 1016 trial was pretty definitive that cisplatin is superior. Now, there were subsets in which there was no difference between the arms, and I think we still have a lot of work to do in figuring out how to identify patients who might be able to get away without cisplatin at baseline, but as of now, the standard of care is full-dose radiation with cisplatin.
Dr. Shah: Well, we will stay on top of this. Thank you so much.
Dr. Burtness: Thank you.
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