November 25 2024
Recent results from the Phase II portion of the NRG Oncology NRG-HN004 clinical study showed excellent results for the combination of cetuximab and radiation among patients receiving these interventions in the control arm. The results also indicate that durvalumab is not recommended in place of cetuximab for patients with head and neck cancer who have a contraindication to cisplatin. Patients who received durvalumab adjuvant and concurrently with radiotherapy did not see improvements in survival outcomes when compared to patients receiving cetuximab with radiotherapy. These results were recently published in Lancet Oncology.
“While immune checkpoint inhibitors have shown promise in other clinical studies in the treatment of head and neck cancers for cisplatin ineligible patients due to its common association with lower toxicity, unfortunately this was not a successful treatment option when combined with radiotherapy for patients in the medically frail population with this disease type. This trial highlights the need for continued research and trials to find options that are safe and effective in this population as there currently is no defined standard of care,” stated Loren K. Mell, MD, of the University of California, San Diego and the lead author of the NRG-HN004 manuscript.
NRG-HN004 was designed to address the need for a confirmed standard of care for head and neck cancer patients who are cisplatin-ineligible. Currently, patients who fall into this population are treated with radiotherapy and most commonly cetuximab; however, many study findings have questioned the effectiveness of using cetuximab. The primary objective of the Phase II portion of the NRG-HN004 was to determine if durvalumab with radiotherapy would improve progression-free survival for patients when compared to cetuximab with radiotherapy.
Following a ten-patient safety lead-in, NRG-HN004 randomly assigned 186 patients to receive either durvalumab (123 patients) 2 weeks before then every 4 weeks during radiotherapy for 7 cycles or cetuximab (63 patients) 1 week before then weekly during radiotherapy for 8 cycles. Phase II accrual was suspended in July 2021 following an interim futility analysis and the trial permanently closed in September 2022. Extended follow up data collection concluded in July 2023.
The analysis showed that 2-year progression-free survival rates were 50.6% (95% confidence interval [CI] 41.559.8) in the durvalumab group versus 63.7% (51.3–76.1) in the cetuximab group (hazard ratio [durvalumab/cetuximab] 1.33 [95% CI 0.84–2.12]; p=0.89). These results for cetuximab and radiation are among the highest reported in the medical literature in this patient population. Adverse events were similar in each group. The most common grade 3-4 adverse events included dysphagia (22% in the durvalumab group vs. 30% in the cetuximab group), lymphopenia (28% vs. 33%), and oral mucositis (11% vs. 18%). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events.
This project was supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), and U24CA196067 from the National Cancer Institute (NCI), part of the National Institutes of Health. The study was sponsored by the NCI and durvalumab was provided by AstraZeneca under a Cooperative Research and Development Agreement with NCI. NRG-HN004 was led and conducted by NRG Oncology with participation from NCI funded National Clinical Trials Network.
Citation
Mell LK, Torres-Saavedra PA, Wong SJ, Kish JA, Chang SS, Jordan RC, Liu T, Truong MT, Winquist EW, Takiar V, Wise-Draper T, Robbins JR, Rodriguez CP, Awan MJ, Beadle BM, Henson C, Narayan S, Spencer SA, Powell S, Dunlap N, Sacco AG, Hu KS, Park HS, Bauman JE, Harris J, Yom SS, Le QT. 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. 2024 Nov 14:S1470-2045(24)00507-2. doi: 10.1016/S1470-2045(24)00507-2. Epub ahead of print. PMID: 39551064.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.