Patients with HPV-positive oropharynx cancer should receive chemoradiation

October 22, 2018

Munich, Germany, 22 October 2018 - Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich. (1)

"Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments," said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK.

Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are 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 30-40 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, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.

This study compared side effects and survival with the two treatments in 334 patients with HPV-positive throat cancer 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 two-year study there were ten 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%) than those on cetuximab (89.4%; p=0.001, hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.70-14.67). Cancer was over three times more likely to recur in two years with cetuximab compared to cisplatin, with recurrence rates of 16.1% versus 6.0%, respectively (p=0.0007, HR 3.39, 95% CI 1.61-7.19).

There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3-5) 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.

Mehanna said: "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."

Commenting on the study for ESMO, Dr Branislav Bystricky, Head, Medical and Radiation Oncology Department, University Hospital Trencin, Slovakia, said: "It was believed that cetuximab causes less side effects and was therefore a good option for HPV-positive throat cancer patients who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives 'double' the benefit since it is more effective in terms of survival and does not worsen all grade toxicity compared to cetuximab with radiotherapy."

Bystricky noted that the results were in agreement with interim findings of the US National Cancer Institute's RTOG 1016 trial, which is scheduled to report this month.(2) He said: "We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS-variant can select a group of patients that will benefit from cetuximab treatment with radiotherapy."
Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2018 Congress

Official Congress hashtag: #ESMO18


This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.


  1. Abstract LBA9_PR 'Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy' will be presented by Hisham Mehanna during the Presidential Symposium 3 on Monday, 22 October, 16:30 to 18:00 (CEST) in Room 18 - Hall A2. Annals of Oncology, Volume 29 Supplement 8 October 2018
  2. Full results presented at the plenary session at the American Society for Radiation Oncology (ASTRO) annual meeting on 22 October:

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With 18,000 members representing oncology professionals from over 150 countries worldwide, ESMO is the society of reference for oncology education and information. ESMO is committed to offer the best care to people with cancer, through fostering integrated cancer care, supporting oncologists in their professional development, and advocating for sustainable cancer care worldwide.Visit

LBA9_PR - Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy

H. Mehanna1, A. Kong1, A. Hartley2, P. Mistry3, M. Dalby3, T. Fulton-Lieuw1, M. Robinson4, A. Gray5, B. Foran6, M. Sen7, L. O'Toole8, K. Dyker9, H. Al Booz10, R. Moleron11, S. Brennan12, E. Aynsley13, A. Chan14, D. Srinivasan15, J. Buter16, J. Dunn3

1Institute of Cancer and Genomic Sciences, The University of Birmingham, Birmingham, UK, 2Oncology, Queen Elizabeth Hospital Birmingham, Birmingham, UK, 3Warwick Clinical Trials Unit, University of Warwick, Coventry, UK, 4Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, UK, 5Department of Population Health, University of Oxford, Oxford, UK, 6Oncology, Weston Park Hospital, Sheffield, UK, 7Oncology, St James's Institute of Oncology, Leeds, UK, 8Oncology, Castle Hill Hospital, Cottingham, UK, 9Oncology, Bradford Institute for Health Research, Bradford, UK, 10Oncology, Bristol Haematology and Oncology Centre, Bristol, UK, 11Oncology, NHS Grampian, Aberdeen, UK, 12Radiation Oncology, Saint Luke's Radiation Oncology Network, Dublin, Ireland, 13Oncology, South Tees Hospitals, Middlesborough, UK, 14Oncology, University Hospitals Coventry & Warwickshire, Coventry, UK, 15Oncology, Western General Hospital, Edinburgh, UK, 16Medical Oncology, VU University Medical Center, Amsterdam, Netherlands

Background: The incidence of Human papillomavirus-positive oropharyngeal cancer (HPV+OPSCC) is rapidly rising. It is a distinct disease entity, affecting younger patients, with much better outcomes. However, standard treatment (cisplatin+radiotherapy) causes significant toxicity, which these young patients have to endure for decades. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation to reduce toxicity of standard (cisplatin) treatment, but no randomised trials exist.

Methods: In this international, multi-centre, randomised, controlled trial, patients with low-risk HPV+OPSCC were randomised to receive radiotherapy (70G in 35F) and either cisplatin (3 doses of 100 mg/m2) or cetuximab (400 mg/m2 loading dose followed by weekly 250 mg/m2). Outcomes were total number of severe (Grades 3-5) toxicity events, overall survival, and quality of life.

Results: We recruited 334 patients (166 in cisplatin arm and 168 in cetuximab arm) between November 2012 through October 2016 at 32 head and neck treatment centres in 3 countries: UK, Ireland and the Netherlands. Of patients randomised, 80% are male, mean age 57 years. The arms were well balanced. There were 10 recurrences and 6 deaths in cisplatin arm, compared to 29 recurrences and 20 deaths in cetuximab arm. There was a significant difference in the 2-year overall survival between cisplatin and cetuximab (97.5% vs 89.4% respectively, p=0.001, HR=4.99, 95% CI 1.70-14.67) and in 2-year recurrence rate (6.0% vs 16.1% respectively, p=0.0007, HR=3.39, 95% CI 1.61-7.19). There were no differences between the cisplatin and cetuximab arms in the reported mean number of overall (5.37 vs 5.45 events per patient respectively), acute or late severe (grade 3-5) toxicity events per patient or all grade toxicity (overall 29.15 vs 30.05 event per patients respectively). There were significantly more serious adverse events (162 vs 95) in the cisplatin arm compared to the cetuximab arm.

Conclusions: There was significant detriment from the use of cetuximab instead of cisplatin in terms of tumour control, and no benefit in terms of reduced toxicity. Cisplatin and radiotherapy remains the standard of care in this setting.

Clinical trial identification: ISRCTN33522080

Legal entity responsible for the study: University of Warwick

Funding: Cancer Research UK

Disclosure: H. Mehanna: Honoraria: AstraZeneca. Speakers' Bureau: MSD, Sanofi Pasteur, Merck. Research Funding: GSK Biologicals, MSD, Sanofi Pasteur, Silence Therapeutics, GSK Plc, AZ. Travel Accommodation Expenses: Sanofi Pasteur, MSD, Merck.

A. Kong: I have received research grants from PUMA and AstraZeneca. I have received payments as a speaker, consultant or in an advisory role for the following companies: PUMA, Merck, BMS, MSD and Avvinity Therapeutics Limited.

M. Robinson: Consultancy for Leica Biosystems.

B. Foran: I have received payments from MSD and Merck for speaker engagements.

L. O'Toole: Merck sponsored my trip to ICHNO 2015.

R. Moleron: I hereby declare the receipt of consultation fees from Bristol-Myers-Squibb and MSD.

All other authors have declared no conflicts of interest.

European Society for Medical Oncology

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to