Good morning everybody, I’m presenting the De-ESCALaTE study on behalf of the De-ESCALaTE trial group. These are my disclosures.
Oropharyngeal cancer, that’s cancer of the throat, is increasing rapidly, especially in the Western world. As you can see here on your left this is the incidence of the cancer in the UK: between 1995 and 2005 it’s doubled in instance, between 2005 and 2010 it’s doubled in incidence again, so it’s very rapidly increasing. The reason is due to the increase in human papilloma virus, HPV positive cancers and on your right you can see the incidence for Stockholm of HPV tonsillar cancer going up in black and HPV negative cancer going down.
These patients are usually younger, they’re in their 50s, they’re of higher socioeconomic status, they’re working, usually with younger families and the good news is that they respond well to treatment. But the corollary of that is, of course, that they live for three, four decades after treatment and the treatment has significant toxicity so they have to withstand the treatment effects that are caused by this treatment.
So the De-ESCALaTE study was looking to see whether we have a treatment that could result in reduced toxicity but similar survival and one of these so-called de-escalation strategies was the use of cetuximab, an EGFR inhibitor that is FDA approved in head and neck cancer. Our study was comparing the standard of care, which is cisplatin and radiotherapy, to cetuximab and radiotherapy. Our primary outcome was severe overall toxicity and what we found is that there really was no difference in overall severe toxicity, whether it was acute or late. When you looked at all types of toxicity, so grade 1-5, there still was no difference between cetuximab and cisplatin and therefore that primary outcome did not show any difference. The quality of life was also the same and so was swallowing; swallowing is one of the big effects of treatment but the swallowing was the same between both arms. There were significantly more serious adverse events with cisplatin so cetuximab does result in significantly less serious adverse events.
But really the surprise of the study was in the survival and what we found was a significantly worse survival with cetuximab. In fact, it’s an 8.1% overall survival difference between the two arms and a hazard ratio of 4.99. The numbers needed to treat to cause harm was 12 so for every twelve patients one didn’t do as well if they were treated with cetuximab. That was driven mainly by both a difference in local regional control and a difference in distant control, so in distant metastasis as well.
So our study has concluded that in comparison to cisplatin in this low risk HPV positive subgroup of patients, or group of patients, cetuximab results in the same severe toxicity, in the same quality of life and swallowing, less serious adverse events but, importantly, worse survival and worse local regional and distant control. Therefore cisplatin still remains the standard of care in this low risk, good prognosis group of patients.
I’m glad to report that the paper has been accepted by The Lancet and it should be available online in the next couple of weeks. Thanks.