Oropharyngeal cancer, which is throat cancer, is increasing rapidly around the world, especially in the Western world. That’s mainly due to the human papilloma virus that has been increasing in the last couple of decades, for example in the UK incidence has doubled between 1995 and 2005 and it’s doubled again between 2005 and 2010. It appears that HPV oropharyngeal cancer is a distinct disease entity – it affects younger patients, they’re usually of higher socioeconomic status. It has a link with oral sex and with an increased number of sexual partners but the good news is that patients with HPV oropharyngeal cancer do really well on treatment. The bad news is, of course, they survive longer, they have significant toxicity from the treatment. So there is wide consensus around the world that we need to find better treatments or less toxic treatments and that’s why we looked at the study and did the study.
How many patients were recruited?
334 patients were recruited in this study.
Any pre-treatment? Any other lines of therapy?
No, this is in the curative setting, they were all p16 positive, low risk, HPV positive patients with oropharyngeal cancer.
What was the treatment schedule?
Patients all got 70Gy in 35 fractions in terms of radiotherapy and they were randomised either to cisplatin100mg/m2 three-weekly or cetuximab, they got a loading dose and then weekly cetuximab after that during the radiotherapy.
When it comes to the results, the toxicity being a primary endpoint?
That’s right and the primary endpoint was overall toxicity, overall severe toxicity as graded by the CTCAE system. We found that there were exactly the same toxicity rates in both arms; that didn’t differ whether it was acute toxicity or late toxicity. We also looked at all grade toxicities, so grade 1-5, and it was the same in both arms as well.
What’s the length of follow-up they’ll be tracking patients for survival?
We tracked them for a minimum of two years, some of them have had significantly longer, and the really surprising finding was that patients on cetuximab had significantly worse survival compared to patients on cisplatin. There was a 7% difference in overall survival, a hazard ratio of 4.99 and the number needed to treat to cause harm was 12 so it was quite a high number.
That’s fairly conclusive findings for cetuximab.
Yes, unfortunately that was the case. We had hoped that it would result in similar survival but less toxicity but that hasn’t been the case.
What next for treating oropharyngeal cancer?
There are several other strategies that are being studied at the moment for de-escalation but on the basis of the results that we have shown, because of the fact that cetuximab resulted in higher local regional recurrence and also a higher rate of distant metastasis, we need to be cautious about de-escalating regimens that don’t include systemic therapies because of the effect on distant metastasis. Therefore we need to consider carefully the de-escalation strategies that we are undergoing at the moment.
If I could also pick your brains for just a few minutes about the role of HPV vaccination in disease prevention across England and also globally.
Yes, as you know, HPV vaccination in the UK has been very successful in girls, we’ve had very wide coverage and there was a question as to whether vaccinating boys will be of additional benefit to the population as a whole. The question is still open in terms of conclusivity but what is becoming more obvious is that as the rate of oropharyngeal HPV cancer increases the cost effectiveness of vaccination improves. Just recently the Joint Committee on Vaccination and Immunisation in the UK has recommended extending vaccination to boys as well as girls which is good news.
This is even more of an issue in countries where there isn’t a high coverage of vaccination in girls because then there isn’t any opportunity for herd immunity and therefore both boys and girls are not protected and therefore immunisation is even more important for boys in that setting.
