PMID- 33125944
OWN - NLM
STAT- MEDLINE
DCOM- 20210219
LR  - 20210219
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 141
DP  - 2020 Dec
TI  - Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced 
      squamous-cell carcinoma of the head and neck: The safety phase of a randomised 
      phase III trial GORTEC 2017-01 (REACH).
PG  - 21-29
LID - S0959-8049(20)30491-3 [pii]
LID - 10.1016/j.ejca.2020.09.008 [doi]
AB  - BACKGROUND: Based on the hypothesis of synergistic effect of avelumab with 
      cetuximab and radiotherapy, this new combination is tested in a randomised trial 
      against two well-established standard of care (SOC) in locally advanced 
      squamous-cell carcinoma of the head and neck (LA-SCCHN). METHODS: This phase III 
      trial comprises two cohorts of patients deemed fit to receive cisplatin 
      (100 mg/m(2) Q3W) (cohort 1) or unfit to cisplatin (cohort 2). The SOC was 
      Intensity Modulated Radiation Therapy (IMRT) with cisplatin in cohort 1 (arm A) 
      and with weekly cetuximab in cohort 2 (arm D). In both cohorts, experimental arms 
      (arms B and C) were IMRT with cetuximab and avelumab (10 mg/kg day 7 and every 2 
      weeks) followed by avelumab every two weeks for 12 months. A safety phase was 
      planned among the first 41 patients in experimental arms by monitoring grade >/=IV 
      adverse events (AEs) with an unacceptable rate of 35%. RESULTS: Between September 
      2017 and August 2018, 82 patients with LA-SCCHN were randomised including 41 
      patients in experimental arms. All patients of experimental arms except one (arm 
      C) received entire radiotherapy as planned. Most common grade >/=III AEs were 
      mucositis, radio-dermatitis, and dysphagia. Grade >/=IV AEs occurred in 5/41 (12%) 
      patients, all in arm C (no grade V). This rate was acceptable according to the 
      hypotheses of the safety phase. In the SOC arms, grade >/=IV AEs occurred in 3/21 
      patients (14%) in arm A and 2/20 (10%) in arm D. One grade V haemorrhage occurred 
      in arm A. CONCLUSION: The avelumab-cetuximab-RT combination was tolerable for 
      patients with LA-SCCHN, and the approval was given for continuing the trial 
      without modification. CLINICALTRIAL.GOV: NCT02999087.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Tao, Yungan
AU  - Tao Y
AD  - Gustave-Roussy Institute, Villejuif, France.
FAU - Auperin, Anne
AU  - Auperin A
AD  - Gustave-Roussy Institute, Villejuif, France.
FAU - Sun, Xushan
AU  - Sun X
AD  - Hopital Nord Franche-Comte de Montbeliard & CHRU de Besancon, France.
FAU - Sire, Christian
AU  - Sire C
AD  - Centre Hospitalier de Lorient, France.
FAU - Martin, Laurent
AU  - Martin L
AD  - Centre Guillaume le Conquerant, Le Havre, France.
FAU - Coutte, Alexandre
AU  - Coutte A
AD  - CHU, Amiens, France.
FAU - Lafond, Cedrik
AU  - Lafond C
AD  - Centre Jean Bernard, Le Mans, France.
FAU - Miroir, Jessica
AU  - Miroir J
AD  - Centre Jean Perrin, Clermont-Ferrand, France.
FAU - Liem, Xavier
AU  - Liem X
AD  - Centre Oscar Lambret, Lille, France.
FAU - Rolland, Frederic
AU  - Rolland F
AD  - ICO Rene-Gauducheau, Nantes, France.
FAU - Even, Caroline
AU  - Even C
AD  - Gustave-Roussy Institute, Villejuif, France.
FAU - Nguyen, France
AU  - Nguyen F
AD  - Gustave-Roussy Institute, Villejuif, France.
FAU - Saada, Esma
AU  - Saada E
AD  - Centre Antoine Lacassagne, Nice, France.
FAU - Maillard, Aline
AU  - Maillard A
AD  - Gustave-Roussy Institute, Villejuif, France.
FAU - Colin-Batailhou, Natacha
AU  - Colin-Batailhou N
AD  - GORTEC, Tours, France.
FAU - Thariat, Juliette
AU  - Thariat J
AD  - Centre Francois Baclesse, Caen, France.
FAU - Guigay, Joel
AU  - Guigay J
AD  - Centre Antoine Lacassagne, Nice, France.
FAU - Bourhis, Jean
AU  - Bourhis J
AD  - CHUV Lausanne, Switzerland. Electronic address: jean.bourhis@chuv.ch.
LA  - eng
SI  - ClinicalTrials.gov/NCT02999087
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20201024
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - KXG2PJ551I (avelumab)
RN  - PQX0D8J21J (Cetuximab)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - Cetuximab/*adverse effects
MH  - Chemoradiotherapy/*adverse effects/methods
MH  - Cisplatin/adverse effects
MH  - Female
MH  - Head and Neck Neoplasms/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Squamous Cell Carcinoma of Head and Neck/*therapy
OTO - NOTNLM
OT  - Avelumab-cetuximab-radiotherapy
OT  - Head and neck
OT  - Locally advanced squamous cell carcinoma
OT  - Safety phase
COIS- Conflict of interest statement All authors declare no conflict of interest.
EDAT- 2020/10/31 06:00
MHDA- 2021/02/20 06:00
CRDT- 2020/10/30 20:09
PHST- 2020/04/15 00:00 [received]
PHST- 2020/08/18 00:00 [revised]
PHST- 2020/09/03 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/10/30 20:09 [entrez]
AID - S0959-8049(20)30491-3 [pii]
AID - 10.1016/j.ejca.2020.09.008 [doi]
PST - ppublish
SO  - Eur J Cancer. 2020 Dec;141:21-29. doi: 10.1016/j.ejca.2020.09.008. Epub 2020 Oct 
      24.