A randomized, placebo-controlled, phase II study of docetaxel and platinum with or without erlotinib in recurrent/metastatic head and neck squamous-cell carcinomas.
8 affiliations
- 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Medical Oncology, Oncoclínicas, São Paulo, Brazil; Department of Oncology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Electronic address: [email protected].
- 2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
- 3Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
- 4Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, USA.
- 5Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Internal Medicine, The University of Texas at Tyler, Tyler, USA.
- 6Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, USA.
- 7Department of Oncology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Department of Head and Neck Surgery, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
- 8Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Medical Oncology and Therapeutics Research, City of Hope Duarte Cancer Center, Duarte, USA.
Abstract
Purpose
We conducted a randomized phase II trial to evaluate whether adding erlotinib to platinum/docetaxel improves clinical outcomes in the first-line treatment of recurrent or metastatic head and neck squamous-cell carcinomas, building on our previous single-arm phase II trial.Patients and methods
This was a placebo-controlled, double-blind, single-center phase II study. Patients (N = 120) were randomly assigned (1 : 1) to receive platinum (carboplatin area under the curve 6 or cisplatin 75 mg/m² every 21 days for six cycles) plus docetaxel (75 mg/m² every 21 days for six cycles) with either erlotinib (150 mg/day orally until progression) or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rates, duration of response, and correlations of erlotinib-induced rash/biomarkers with outcomes.Results
Median PFS was 6.1 months with erlotinib versus 4.4 months with placebo [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.42-0.95, P = 0.026]. Median overall survival was 17.0 months in the erlotinib arm compared with 13.7 months in the control arm (HR 0.67, 95% CI 0.43-1.04, P = 0.0718), meeting the prespecified type I error threshold. Subgroup analyses demonstrated numerically favorable PFS HRs across most clinical subgroups, with a more pronounced benefit observed in patients with oropharyngeal and human papillomavirus-related tumors. Development of grade ≥2 rash during the first cycle of erlotinib was associated with significantly improved overall survival (HR 0.40, 95% CI 0.19-0.87, P = 0.021). The addition of erlotinib increased the incidence of grade 2-4 adverse events, particularly gastrointestinal toxicity, rash, fatigue, and dehydration but no unexpected safety signals were observed.Conclusions
The study met its primary endpoint, supporting the continued relevance of epidermal growth factor receptor (EGFR) inhibition in this disease. Although contemporary immunotherapy-based standards limit direct adoption of this regimen, these results provide clinically meaningful insight into EGFR biology and support further development of modernized, tyrosine kinase inhibitor-based EGFR strategies, including rational combinations and biomarker-driven approaches, to improve outcomes.
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BibTeX
@article{william2026randomized,
title = {{A randomized, placebo-controlled, phase II study of docetaxel and platinum with or without erlotinib in recurrent/metastatic head and neck squamous-cell carcinomas.}},
author = {W N William and L Feng and M S Kies and S Ahmed and G R Blumenschein and B S Glisson and E Massarelli and F M Johnson and C Lu and X Le and L P Kowalski and E S Kim},
journal = {ESMO open},
year = {2026},
month = oct,
doi = {10.1016/j.esmoop.2026.108584},
url = {https://europepmc.org/article/MED/42868984},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A randomized, placebo-controlled, phase II study of docetaxel and platinum with or without erlotinib in recurrent/metastatic head and neck squamous-cell carcinomas.
AU - W N William
AU - L Feng
AU - M S Kies
AU - S Ahmed
AU - G R Blumenschein
AU - B S Glisson
AU - E Massarelli
AU - F M Johnson
AU - C Lu
AU - X Le
AU - L P Kowalski
AU - E S Kim
PY - 2026
DA - 2026/10/13
JO - ESMO open
DO - 10.1016/j.esmoop.2026.108584
UR - https://europepmc.org/article/MED/42868984
AB - Purpose We conducted a randomized phase II trial to evaluate whether adding erlotinib to platinum/docetaxel improves clinical outcomes in the first-line treatment of recurrent or metastatic head and neck squamous-cell carcinomas, building on our previous single-arm phase II trial.Patients and methods This was a placebo-controlled, double-blind, single-center phase II study. Patients (N = 120) were randomly assigned (1 : 1) to receive platinum (carboplatin area under the curve 6 or cisplatin 75 mg/m² every 21 days for six cycles) plus docetaxel (75 mg/m² every 21 days for six cycles) with either erlotinib (150 mg/day orally until progression) or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rates, duration of response, and correlations of erlotinib-induced rash/biomarkers with outcomes.Results Median PFS was 6.1 months with erlotinib versus 4.4 months with placebo [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.42-0.95, P = 0.026]. Median overall survival was 17.0 months in the erlotinib arm compared with 13.7 months in the control arm (HR 0.67, 95% CI 0.43-1.04, P = 0.0718), meeting the prespecified type I error threshold. Subgroup analyses demonstrated numerically favorable PFS HRs across most clinical subgroups, with a more pronounced benefit observed in patients with oropharyngeal and human papillomavirus-related tumors. Development of grade ≥2 rash during the first cycle of erlotinib was associated with significantly improved overall survival (HR 0.40, 95% CI 0.19-0.87, P = 0.021). The addition of erlotinib increased the incidence of grade 2-4 adverse events, particularly gastrointestinal toxicity, rash, fatigue, and dehydration but no unexpected safety signals were observed.Conclusions The study met its primary endpoint, supporting the continued relevance of epidermal growth factor receptor (EGFR) inhibition in this disease. Although contemporary immunotherapy-based standards limit direct adoption of this regimen, these results provide clinically meaningful insight into EGFR biology and support further development of modernized, tyrosine kinase inhibitor-based EGFR strategies, including rational combinations and biomarker-driven approaches, to improve outcomes.
SN - 2059-7029
ER -