Amended Trial: David Sher Gives an Update on the EA3211 Trial for Patients with Metastatic Squamous Cell Carcinoma of the Head and Neck

By David J. Sher, MD, MPH

@DavidSherMD

In the last 5 years, the use of anti-PD1/PD-L1 immunotherapies (e.g., nivolumab and pembrolizumab) has greatly improved clinical outcomes for patients with metastatic head and neck squamous cell carcinoma (mHNSCC). However, there is still room for significant improvement in treatment and survival outcomes, as the two-year survival rate for patients with mHNSCC is only about 30%. Locoregional progression of this disease can also lead to difficult symptoms and consequential decreases in patients’ quality of life. Several recent studies have shown that deploying radiotherapy to primary and metastatic sites can lead to pronounced improvements in overall survival (OS) and clinical outcomes for mHNSCC patients.

EA3211’s primary objective is to compare OS between patients receiving immunotherapy plus consolidative radiotherapy (CoRT) vs. patients receiving immunotherapy alone, after initial systemic chemoimmunotherapy. The study hypothesizes that the addition of CoRT to the metastatic deposits +/- the primary site (if active and unirradiated) will improve OS by reducing locoregional/in-field progression and eradicating potential sources of treatment-resistant disease. If the hypothesis is supported by the study data, EA3211 could be a practice-changing study indicating the use of radiotherapy in treating patients with mHNSCC. EA3211’s Amendment #5 (v.01/02/25) was recently activated, with significant updates to help the study reach its accrual goal of 290 participants.

Amendment #5 was recently activated (v.01/02/25); important updates include:

• A newly defined study cohort (Cohort M) expands eligibility to include patients with metachronous disease, defined as active disease only in distant sites with no evidence of locoregional recurrence, with primary head/neck therapy completed ≥ 6 months prior to registration
  • Changes have been made throughout the protocol to reflect the new cohort and the original cohort (Cohort S); please carefully review the updated eligibility criteria (Section 3) and treatment plans for each (Section 5)
  • Note that Cohorts M and S are separate from Arms S and T
• Other key updates:
  • Clarified definition of the number of metastatic sites as number of isocenters required to treat metastatic disease (criterion 3.1.6)
  • Clarified Step 1 Option 3 treatment plan: 5-FU (1000 mg/m²) is administered as a continuous infusion (Section 5.1.1)
  • Addition of palliative radiotherapy option (Section 5.2.6)
  • Updated expedited AE reporting procedures (Section 5.3)
  • Clarification of health-related quality of life (HRQL) assessment schedule and expanded window for completion of HRQL instruments to +/- 3 weeks (Section 5.7.2)
• Updates to the Informed Consent Document

Please note that this is not a complete list of this amendment’s updates; please review the protocol for all changes. Study resources have been revised to reflect Amendment #5, and are available for download at CTSU.org or on the EA3211 Educational Materials page.

Learn more about EA3211 at ecog-acrin.org.

Dr. Sher (UT Southwestern Medical Center) is the study chair for this trial. The study co-chair is Jessica R. Bauman, MD (Fox Chase Cancer Center).