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

Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):462-472. doi: 10.1016/j.ijrobp.2016.10.011. Epub 2016 Oct 20.

Abstract

Purpose: 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.

Methods and materials: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / adverse effects
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Cetuximab / adverse effects
  • Cetuximab / therapeutic use*
  • Chemoradiotherapy / methods*
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16*
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / complications*
  • Sample Size
  • Smoking / adverse effects
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Cetuximab
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT01216020