title: Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer.
abstract: We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer.
  
  
  
  The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions.
  
  
  
  A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm.
  
  
  
  In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy. Electronic address: michela.buglione@unibs.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Buglione
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Maddalo
authors.affiliation: Department of Radiation Oncology, IRCCS San Martino, IST National Cancer Research Institute and University, Genova, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvò
authors.affiliation: Department of Radiation Oncology, University of Siena, Siena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
authors.affiliation: Department of Radiation Oncology, Azienda Ospedaliero, Universitaria Careggi, Firenze, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paiar
authors.affiliation: Department of Radiation Oncology, San Donato Hospital, Arezzo, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Lastrucci
authors.affiliation: Department of Radiation Oncology, Pistoia Hospital, Pistoia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Stefanacci
authors.affiliation: Department of Radiation Oncology, IRCCS San Martino, IST National Cancer Research Institute and University, Genova, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Belgioia
authors.affiliation: Department of Radiation Oncology, University of Siena, Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Crociani
authors.affiliation: Department of Medical Oncology, IRCCS San Martino, IST National Cancer Research Institute and University, Genova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Vecchio
authors.affiliation: Department of Radiation Oncology, Azienda Ospedaliero, Universitaria Careggi, Firenze, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonomo
authors.affiliation: Department of Radiation Oncology, San Donato Hospital, Arezzo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bertocci
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Borghetti
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Pasinetti
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Triggiani
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Costa
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Tonoli
authors.affiliation: Department of Medical Oncology, Brescia University, Brescia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.affiliation: Department of Radiation Oncology, Brescia University, Istituto del Radio "O. Alberti," Spedali Civili Hospital, Brescia, Italy.
authors.forename: Stefano Maria
authors.initials: SM
authors.lastname: Magrini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D018401:Sample Size; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab; D002945:Cisplatin