Provide a concise summary of the RTOG 0920 trial evaluating postoperative intensity‑modulated radiation therapy with weekly cetuximab versus radiation alone in resected intermediate‑risk head‑and‑neck squamous cell carcinoma.

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Last updated: February 10, 2026 • View editorial policy

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RTOG 0920 Trial Overview

RTOG 0920 is a phase 3 randomized trial comparing postoperative intensity-modulated radiation therapy (IMRT) plus weekly cetuximab versus IMRT alone in patients with completely resected, intermediate-risk head and neck squamous cell carcinoma, which demonstrated significant improvement in disease-free survival but not overall survival, with the benefit limited to HPV-negative patients. 1

Trial Design and Patient Population

  • Eligibility criteria: Patients with completely resected squamous cell carcinoma of the oral cavity, oropharynx, or larynx with one or more intermediate-risk factors warranting postoperative radiotherapy 1
  • Randomization: 1:1 assignment to IMRT (60-66 Gy) with weekly cetuximab versus IMRT alone 1
  • Enrollment: 702 patients enrolled from November 2009 to March 2018, with 577 randomly assigned and eligible for analysis 1
  • Patient characteristics: Most patients (63.6%) had oral cavity cancer, and the majority (84.6%) had high EGFR expression 1
  • HPV status: 80.2% of patients in the trial were HPV-negative 1

Primary and Secondary Endpoints

  • Primary endpoint: Overall survival (OS) in the randomly assigned/eligible population, with a prespecified secondary analysis in the HPV-negative subpopulation 1
  • Secondary endpoints: Disease-free survival (DFS) and toxicity 1

Key Efficacy Results

Overall Survival (Primary Endpoint)

  • Median follow-up: 7.2 years with fewer deaths (184) than expected 1
  • OS results: Not significantly improved with RT + cetuximab (HR 0.81; one-sided P = 0.0747) 1
  • 5-year OS: 76.5% (RT + cetuximab) versus 68.7% (RT alone) 1

Disease-Free Survival (Secondary Endpoint)

  • DFS results: Significantly improved with RT + cetuximab (HR 0.75; one-sided P = 0.0168) 1
  • 5-year DFS: 71.7% (RT + cetuximab) versus 63.6% (RT alone) 1

HPV-Negative Subgroup Analysis

  • Critical finding: The benefit of RT + cetuximab was only observed in the HPV-negative subpopulation, which comprised 80.2% of trial patients 1

Toxicity Profile

Acute Toxicity

  • Grade 3-4 acute toxicity: 70.3% (RT + cetuximab) versus 39.7% (RT alone), with statistically significant difference (two-sided P < 0.0001) 1
  • Primary acute toxicities: Predominantly skin and/or mucosal effects 1

Late Toxicity

  • Grade ≥3 late toxicity: 33.2% (RT + cetuximab) versus 29.0% (RT alone), with no statistically significant difference (two-sided P = 0.3101) 1
  • Grade 5 toxicity: None observed in either treatment arm 1

Clinical Context and Implications

This trial addresses the intermediate-risk population, which differs from the high-risk population studied in RTOG 9501 and EORTC 22931 trials that established cisplatin-based chemoradiotherapy as standard for patients with positive margins and/or extracapsular extension. 2, 3

Positioning in Treatment Landscape

  • RTOG 0920 specifically enrolled patients at intermediate risk of disease recurrence who underwent surgical resection, regardless of cisplatin eligibility 2
  • The trial's primary endpoint was OS, with data initially expected at the end of 2024 2
  • This represents one of only two phase 3 studies enrolling patients regardless of cisplatin eligibility in the postoperative adjuvant setting 2

Clinical Recommendation

RT + cetuximab is an appropriate treatment option for carefully selected patients with HPV-negative, intermediate-risk, resected head and neck squamous cell carcinoma who cannot tolerate cisplatin-based therapy. 1

Important Caveats

  • Patient selection is critical: The benefit is limited to HPV-negative disease, and the significantly increased acute toxicity (70.3% vs 39.7% grade 3-4) requires careful consideration 1
  • Acute toxicity burden: The substantial increase in acute skin and mucosal toxicity necessitates close monitoring by an experienced multidisciplinary team 1
  • Long-term safety: The lack of increased late toxicity (33.2% vs 29.0%) and absence of grade 5 toxicities in either arm provides reassurance for long-term safety 1
  • OS versus DFS: While DFS was significantly improved, the primary endpoint of OS was not met, which may influence treatment decisions in individual patients 1

References

1
Research

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025

2
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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