Durvalumab plus intensity-modulated radiotherapy (IMRT) proved no more effective than cetuximab plus IMRT in patients with treatment-naïve, locoregionally advanced head and neck squamous cell carcinoma (HNSCC), according to research presented at the 2022 ASTRO Annual Meeting. 

The phase 2/3 trial showed that progression-free survival (PFS) and overall survival (OS) were similar with durvalumab and cetuximab. However, the rate of locoregional failure (LRF) was higher with durvalumab.

This trial (NRG-HN004; ClinicalTrials.gov Identifier: NCT03258554) included 186 patients with previously untreated HNSCC who were ineligible for cisplatin. At baseline, the median age was 72 years, 95% of patients had at least 3 comorbidities, and 84% had an absolute contraindication to cisplatin. T3-4 disease was present in 58% of patients, 49% of patients had N2-3 disease, and 47% had p16-positive disease. 

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The patients were randomly assigned to receive durvalumab plus IMRT (n=123) or cetuximab plus IMRT (n=63). The rate of treatment completion was 61% for all 7 cycles of durvalumab and 81% for at least 7 cycles of cetuximab. The rate of IMRT completion was 87% in the durvalumab arm and 89% in the cetuximab arm.

The primary endpoint was PFS for the phase 2 portion of the trial and OS for the planned phase 3 portion. After an interim futility analysis, the trial was closed to accrual, and it will not proceed to phase 3.

At a median follow-up of 1.2 years, PFS, OS, and distant metastasis were similar between the treatment arms. The 2-year PFS rate was 51% with durvalumab and 66% with cetuximab (hazard ratio [HR], 1.47; 95% CI, 0.86-2.52; P =.92). 

The 2-year OS rate was 70% with durvalumab and 78% with cetuximab (HR, 1.21; 95% CI, 0.63-2.31; P =.72). The 2-year rate of distant metastasis was 9% in the durvalumab arm and 11% in the cetuximab arm (HR, 0.76; 95% CI, 0.27-2.15; P =.61).

Patients who received durvalumab had a higher rate of LRF. The 2-year LRF rate was 32% in the durvalumab arm and 15% in the cetuximab arm (HR, 2.17; 95% CI, 1.00-4.69; P =.04). 

Grade 3 or higher adverse events occurred in 79% of patients in the cetuximab arm and 69% of patients in the durvalumab arm. Dysphagia, mucositis, and dermatitis occurred more frequently with cetuximab.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mell LK, Torres-Saavedra P, Wong S, et al. Radiotherapy with durvalumab vs. cetuximab in patients with locoregionally advanced head and neck cancer and a contraindication to cisplatin: Phase II results of NRG-HN004. ASTRO 2022. October 23-26, 2022. Abstract LBA 02.