학술논문
Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial
Document Type
Academic Journal
Author
Mehanna, Hisham; Robinson, Max; Hartley, Andrew; Kong, Anthony; Foran, Bernadette; Fulton-Lieuw, Tessa; Dalby, Matthew; Mistry, Pankaj; Sen, Mehmet; O'Toole, Lorcan; Al Booz, Hoda; Dyker, Karen; Moleron, Rafael; Whitaker, Stephen; Brennan, Sinead; Cook, Audrey; Griffin, Matthew; Aynsley, Eleanor; Rolles, Martin; De Winton, Emma; Chan, Andrew; Srinivasan, Devraj; Nixon, Ioanna; Grumett, Joanne; Leemans, C Rene; Buter, Jan; Henderson, Julia; Harrington, Kevin; McConkey, Christopher; Gray, Alastair; Dunn, Janet; McArdle, Orla; Husband, David; Loo, Vivienne; Soe, Win; Sridhar, Thiagarajan; Jankowska, Petra; Joseph, Mano; Geropantas, Konstantinos; Vaidya, Deepali; Vijayan, Rengarajan; Hwang, David; Pettit, Laura; Mendes, Ruheena; Forster, Martin; Evans, Mererid; Foran, Bernie; Nankivell, Paul; Bryant, Jennifer; Sharma, Neil; Spruce, Rachel; Brooks, Jill; Batis, Nikos; Roques, Tom; Bidmead, Margaret; Yang, Huiqi; Nutting, Christopher; Tyler, Justine; Baines, Helen; Gasnier, Anne; Miles, Elizabeth; Clark, Catharine
Source
The Lancet. Jan 5, 2019, Vol. 393 Issue 10166, 51
Subject
Language
English
ISSN
0140-6736
Abstract
Summary Background The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. Methods We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of Findings Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3--5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4*8 [95% CI 4*2--5*4] with cisplatin vs 4*8 [4*2--5*4] with cetuximab; p=0*98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29*2 [95% CI 27*3--31*0] with cisplatin vs 30*1 [28*3--31*9] with cetuximab; p=0*49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97*5% vs 89*4%, hazard ratio 5*0 [95% CI 1*7--14*7]; p=0*001) and 2-year recurrence (6*0% vs 16*1%, 3*4 [1*6--7*2]; p=0*0007). Interpretation Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. Funding Cancer Research UK.