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

Date 22 October 2018
Event ESMO 2018 Congress
Session Presidential Symposium 3
Topics Anticancer Agents
Radiation Oncology
Head and Neck Cancers
Presenter Hisham Mehanna
Authors 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. Dunn17
  • 1Institute Of Cancer And Genomic Sciences, The University of Birmingham, B15 2TT - Birmingham/GB
  • 2Oncology, Queen Elizabeth Hospital Birmingham, B15 - Birmingham/GB
  • 3Warwick Clinical Trials Unit, University of Warwick, CV4 - Coventry/GB
  • 4Centre For Oral Health Research, Newcastle University, NE2 - Newcastle-upon-Tyne/GB
  • 5Department Of Population Health, University of Oxford, OX3 - Oxford/GB
  • 6Oncology, Weston Park Hospital, Sheffield/GB
  • 7Oncology, St James's Institute of Oncology, Leeds/GB
  • 8Oncology, Castle Hill Hospital, HU16 - Cottingham/GB
  • 9Oncology, Bradford Institute for Health Research, Bradford/GB
  • 10Oncology, Bristol Haematology and Oncology Centre, Bristol/GB
  • 11Oncology, NHS Grampian, Aberdeen/GB
  • 12Radiation oncology, Saint Luke's Radiation oncology Network, Dublin/IE
  • 13Oncology, South Tees Hospitals, Middlesborough/GB
  • 14Oncology, University Hospitals Coventry & Warwickshire, Coventry/GB
  • 15Oncology, Western General Hospital, Edinburgh/GB
  • 16Medical Oncology, VU University Medical Center, Amsterdam/NL
  • 17Warwick Clinical Trials Unit, University of Warwick, CV4 7AL - Coventry/GB

Abstract

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

Editorial Acknowledgement