ASTRO 2015

Deintensified chemoradiation for HPV-associated oropharyngeal cancer

Dr Bhishamjit Chera - University of North Carolina at Chapel Hill, Chapel Hill, USA

HPV related squamous cell carcinoma of the oropharynx is not a very common cancer when you compare it to breast or prostate or lung cancers, however, there are probably 20,000 cases in the United States every year, thereabouts. But the incidence is increasing and there has been some research that has shown that the incidence is rapidly increasing. We think that the culprit in all of this is the infection with the human papilloma virus in the oropharynx area.

What are the current treatment options?

Most institutions have adopted an organ preservation approach with standard chemoradiotherapy. The standard chemoradiotherapy doses are a seven week course of radiation and chemotherapy given together, the radiation total dose over this seven weeks is 70Gy and the typical most common chemotherapy drug used is cisplatin at a 100mg/m2 given three doses, so a total dose of 300mg/m2.

What was the rationale for using a reduced intensity chemoradiotherapy regimen?

We know the incidence of this cancer is increasing. The other interesting thing with this is that people who have HPV, if we find HPV in their tumour in their oropharynx, they actually have a very good chance of being cured with standard chemotherapy and radiation regimens. However, the long-term side effects are pretty significant. So there’s a good cost to getting cured with standard treatment.

Can you outline the study design and methods and patient population of the phase II study?

What we did is we were interested in studying reduced dose radiation and chemotherapy in these patients. So what we did is we did a single arm phase II study and all patients got reduced intensity, or deintensified, chemoradiotherapy. So instead of giving the standard 70Gy we gave 60Gy and instead of giving the standard high dose cisplatin at 300mg/m2 we gave 180mg/m2 divided throughout a six week course of radiation and chemotherapy. Then, after they went through this deintensified treatment, we did biopsies of where the cancer was to verify if the cancer was completely gone.

How effective was the deintensified chemoradiotherapy regimen?

The way we judged the effectiveness of it was by those biopsies. So the primary endpoint in the study was the pathological complete response rate, meaning how many of those biopsies were negative and did not show cancer. In 86% of the patients there was no cancer in the biopsies, so that was 43 patients total in the study. So six patients had biopsies proving cancer and those patients we observed them and none of these patients, whether they had a biopsy negative or biopsy positive had cancer recurrence.

How did the two radiotherapy methods used compare?

Actually they’re very similar, it’s the same technology, it’s the same radiation per day at 2Gy per day, it’s just that instead of giving seven weeks of 70Gy we gave six weeks of 60Gy. This 10Gy reduction should result in reduced side effects so we did observe reduced side effects in these patients. Very few patients needed feeding tubes to get through treatment and no patient needed a long-term feeding tube. When we asked the patients about their swallowing they reported that this regimen, this deintensified regimen, really didn’t affect their swallowing.

What did you see in terms of patient quality of life and at what duration of follow up?

The median follow up for our patients was 21 months. The majority of patients have had at least one year of follow up and we’ve asked our patients to give us a lot of quality of life in patient reported outcomes data. Their quality of life is returning to baseline by one year. When you look at the reports of swallowing quality of life, actually the swallowing quality of life didn’t change. Dry mouth is, of course, another major problem these patients have and their dry mouth from the radiation is also recovering over time.

What can be concluded from these data?

This shows strong preliminary evidence that we’re probably over-treating these patients. Our data supports the idea that we can reduce the intensity and possibly maintain high cancer cure rates and control rates and reduce side effects. At this time, though, this should not become the standard of care. We need to treat more patients on controlled clinical trials that study this regimen and we’re doing that at UNC ongoing. Hopefully with more follow-up we’ll be able to show this is efficacious and safe.

What are your future research plans?

We have already conducted or are about to finish conducting a second phase II study in which we have deintensified with the same chemotherapy and radiation regimen but surgery or biopsies are not mandated. There are about 60 patients, we’re going to close that study soon. Then we have a third generation study that’s coming out where we actually use cancer genetics, meaning that we’re going to take the initial diagnostic biopsies from the patient and look at the genetics and try to see if the genetics can help tell us whether it’s safe to deintensify chemotherapy radiation in them.

Do you have a take home message?

Most cancer clinical trials are trying to increase the intensity of treatment, to increase cure rates. In this very favourable subset of patients we are reducing the intensity. So we’re improving the therapeutic ratio by reducing the intensity of treatment which hopefully will result in lower side effects in the long run for these patients.