As reported in The Lancet Oncology by Mell et al, the phase II/III NRG-HN004 trial of radiotherapy with durvalumab or cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma and contraindications for cisplatin was stopped for futility during phase II; the phase III portion of the trial was not performed.
Study Details
In the phase II portion of the North American multicenter open-label trial, 186 eligible patients were randomly assigned 2:1 between March 2019 and July 2021 to receive intensity-modulated radiotherapy at 70 Gy in 35 fractions over 7 weeks plus either durvalumab at 1,500 mg starting 2 weeks before radiotherapy then every 4 weeks starting at week 2 of radiotherapy for 7 cycles (n = 123) or cetuximab at 400 mg/m² 1 week before radiotherapy, then at 250 mg/m² weekly beginning at week 1 of radiotherapy for 8 cycles. The primary endpoint was progression-free survival. At an interim futility analysis, early stopping of the trial was to be considered if a hazard ratio (HR) ≥ 1.0 favoring cetuximab was observed.
Key Findings
Phase II accrual was suspended in July 2021 after an interim futility analysis and permanently closed in September 2022. The phase III portion of the trial was not conducted.
At the protocol-specified analysis, median progression-free survival was 2.2 years (95% confidence interval [CI] = 1.2 years to not reached) in the durvalumab group and 2.7 years (95% CI = 2.7 years to not reached) in the cetuximab group (HR = 1.47, 95% CI = 0.86–2.52, P = .92).
In a post hoc analysis of extended follow-up, with median follow-up of 2.3 years, 2-year progression-free survival was 50.6% (95% CI = 41.5%–59.8%) in the durvalumab group vs 63.7% (95% CI = 51.3%–76.1%) in the cetuximab group (HR = 1.33, 95% CI = 0.84–2.12, P = .89).
The most common grade 3 to 4 adverse events observed in the durvalumab and cetuximab groups were dysphagia (22% vs 30%), lymphopenia (28% vs 33%), and oral mucositis (11% vs 18%). Death due to treatment-related adverse events occurred in four patients (3%) in the durvalumab group (due to death–not otherwise specified, laryngeal edema, lung infection, and respiratory failure) and in one patient (2%) in the cetuximab group (due to death–not otherwise specified).
The investigators concluded: “Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with [head and neck squamous cell carcinoma] with contraindications to cisplatin. Further trials are needed to define the standard of care for this population.”
Loren K. Mell, MD, of the University of California San Diego, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute and AstraZeneca. For full disclosures of the study authors, visit www.thelancet.com.
