Study confirms most effective treatment for HPV-positive throat cancer

Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to research led by BHP founder member the University of Birmingham.

An abstract of the Cancer Research UK-funded study, which was carried out in collaboration with the University of Warwick, was recently delivered at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany.

The trial aimed to compare, for the first time, the outcomes of using two different kinds of treatment for patients with HPV-positive throat cancer – cetuximab and cisplatin.

Study lead Professor Hisham Mehanna, Director of the University of Birmingham’s Institute of Head and Neck Studies and Education, said: “Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as cisplatin chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments.”

Throat cancer is one of the fastest rising cancers in Western countries. In the UK, incidence was unchanged between 1970 and 1995, then doubled between 1996 and 2006, and doubled again between 2006 and 2010. The rise has been attributed to HPV, which is often a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65 to 70 year old working class men. Today HPV is the main cause and patients are aged around 55, middle class, working, and have young children.

HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste.

Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, often receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

The De-ESCALaTE HPV study compared the side effects and survival of 334 patients, 166 of which were treated with radiotherapy and cisplatin and 164 and of whom were given radiotherapy and cetuximab. The patients were enrolled from 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.

During the six-year study there were 10 recurrences and six deaths with cisplatin compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher two-year overall survival rate (97.5 per cent) than those on cetuximab.

Cancer was three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6%, respectively.

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade three to five) toxic events including dry mouth and difficulty swallowing. There were significantly more serious adverse events such as renal and haematological problems with cisplatin than with cetuximab.

Professor Mehanna added: “Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin.

“This was a surprise – we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible.”