Durvalumab Plus Radiotherapy Fails to Improve Survival Outcomes for Cisplatin-Ineligible Patients With Head and Neck Squamous Cell Carcinoma

According to results from the phase 2/3 NRG-HN004 study, durvalumab plus radiotherapy failed to improve survival outcomes compared to cetuximab plus radiotherapy among patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) with a contraindication to cisplatin. 

“Concurrent radiotherapy with cisplatin is standard definitive treatment for locoregionally advanced head and neck squamous cell carcinoma…however, cisplatin is contraindicated in more than a third of patients,” stated Loren Mell, MD, University of California San Diego, La Jolla, California, and coauthors. Here, researchers assess “whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.” 

In this open-label, parallel-group study, following a 10 patient safety lead in, researchers enrolled 190 patients with stage III to IVB p16-negative HNSCC or unfavorable stage I to III p16-positive oropharyngeal or unknown primary carcinoma, with a contraindication to cisplatin. Patients were randomized on a 2-to-1 basis to receive either 1500 mg durvalumab 2 weeks prior to radiotherapy followed by durvalumab every 4 weeks starting week 2 of radiotherapy for 7 cycles (n = 123) or 400 mg/m² of cetuximab 1 week prior to radiotherapy followed by 250 mg/m² of cetuximab starting week 1 of radiotherapy for 8 cycles (n = 63) plus 70 Gy in 35 fractions of intensity-modulated radiotherapy over 7 weeks. Patients were stratified based on stage, performance status, comorbidities, primary site, and p16 status. The phase 2 primary end point was progression-free survival (PFS) in the intention-to-treat population. A key secondary end point was safety. 

At a median follow-up of 2.3 years, the 2-year PFS rate was 50.6% in the durvalumab arm and 63.7% in the cetuximab arm (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.84 to 2.12; P = .89). The most common grade 3/4 adverse events included dysphagia, lymphopenia, and oral mucositis. Four treatment-related deaths occurred in the durvalumab arm, and 1 treatment-related death occurred in the cetuximab arm. 

“The NRG-HN004 phase 2/3 trial was stopped after a planned interim futility analysis [suggesting] that PD-L1 inhibition with durvalumab and radiotherapy was unlikely to improve outcomes over standard cetuximab with radiotherapy for patients with HNSCC and a contraindication to cisplatin,” concluded Dr Mell et al. “Further trials are needed to define the standard of care for this population.” 

Source: 

Mell LK, Torres-Saavedra PA, Wong SJ, et al. Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): An open-label, multicentre, parallel-group, randomised, phase 2/3 trial. Lancet Oncol. Published online: November 14, 2024. doi: 10.1016/S1470-2045(24)00507-2