Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.
Acute Disease
Antineoplastic Agents
/ administration & dosage
Cetuximab
/ administration & dosage
Chemoradiotherapy
/ adverse effects
Cisplatin
/ administration & dosage
Drug Administration Schedule
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
Oropharyngeal Neoplasms
/ pathology
Papillomavirus Infections
/ complications
Radiotherapy, Intensity-Modulated
/ adverse effects
Risk Assessment
Squamous Cell Carcinoma of Head and Neck
/ pathology
Treatment Outcome
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
05 01 2019
05 01 2019
Historique:
received:
11
10
2018
revised:
17
10
2018
accepted:
18
10
2018
pubmed:
20
11
2018
medline:
15
1
2019
entrez:
20
11
2018
Statut:
ppublish
Résumé
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. 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 <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m 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). 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. Cancer Research UK.
Sections du résumé
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 <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m
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.
Identifiants
pubmed: 30449623
pii: S0140-6736(18)32752-1
doi: 10.1016/S0140-6736(18)32752-1
pmc: PMC6319250
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Cetuximab
PQX0D8J21J
Cisplatin
Q20Q21Q62J
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
51-60Subventions
Organisme : Cancer Research UK
ID : 12834
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 16801
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N005872/1
Pays : United Kingdom
Investigateurs
Rafael Moleron
(R)
Orla McArdle
(O)
Karen Dyker
(K)
Hoda Al Booz
(H)
Lorcan O'Toole
(L)
Audrey Cook
(A)
David Husband
(D)
Vivienne Loo
(V)
Win Soe
(W)
Eleanor Aynsley
(E)
Thiagarajan Sridhar
(T)
Petra Jankowska
(P)
Mano Joseph
(M)
Konstantinos Geropantas
(K)
Deepali Vaidya
(D)
Matthew Griffin
(M)
Andrew Hartley
(A)
Rengarajan Vijayan
(R)
David Hwang
(D)
Kevin Harrington
(K)
Laura Pettit
(L)
Stephen Whitaker
(S)
Emma De Winton
(E)
Martin Rolles
(M)
Sinéad Brennan
(S)
Mehmet Sen
(M)
Ruheena Mendes
(R)
Martin Forster
(M)
Andrew Chan
(A)
Mererid Evans
(M)
Jan Buter
(J)
Devraj Srinivasan
(D)
Bernie Foran
(B)
Paul Nankivell
(P)
Jennifer Bryant
(J)
Neil Sharma
(N)
Rachel Spruce
(R)
Jill Brooks
(J)
Nikos Batis
(N)
Tom Roques
(T)
Margaret Bidmead
(M)
Huiqi Yang
(H)
Christopher Nutting
(C)
Justine Tyler
(J)
Julia Henderson
(J)
Helen Baines
(H)
Anne Gasnier
(A)
Elizabeth Miles
(E)
Catharine Clark
(C)
Mererid Evans
(M)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
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