Cetuximab outperforms durvalumab in treatment of head and neck cancers: Lancet

In a clinical trial, Mell and cancer researchers from two dozen other institutions compared the effectiveness of durvalumab and cetuximab-in combination with radiation therapy-in 186 patients with advanced squamous cell carcinoma of the head or neck who were ineligible for cisplatin. They report in The Lancet Oncology that contrary to expectations, cetuximab performed better than durvalumab, with a similar rate of adverse events. As a result, the researchers discontinued the study early. The results were published on November 14, 2024.

“We found that the probability of being alive and free of disease at two years was approximately 64% for cetuximab versus 51% for durvalumab, indicating no evidence of a benefit of durvalumab over cetuximab,” said Mell. “We had a lot of reasons to be optimistic about durvalumab, but it turned out to be potentially worse than the standard.”

Monoclonal antibodies like cetuximab bind to proteins on the surface of cancer cells, halting their growth and proliferation. In contrast, durvalumab, an immune checkpoint inhibitor, blocks a protein on cancer cells called PDL1, which allows tumors to thrive, allowing the immune system’s T cells to attack cancer cells directly. Mell says there is some evidence that durvalumab could still have a place in treating a very specific subset of patients with highly immunoreactive tumors, but more research is needed.

The results have significant implications for the treatment of head and neck cancers. The study-the first of its kind conducted in North America-demonstrated a higher success rate than any previous study of cetuximab in this patient population, and Mell said the drug is likely to become the new standard of care for these patients. The study also revealed that cetuximab showed similar efficacy whether or not a patient’s cancer was associated with HPV.

“Our study helps reinforce that radiation with cetuximab is a very good alternative for patients who cannot get standard cisplatin,” said Mell. “Historically, this has been an underserved group, so our trial sought to establish an evidence base for this rather unique population that skews very much towards older individuals and those with competing health problems that have in many cases been expressly excluded from clinical trials based on those comorbidities.”

Mell says research is in progress to compare cetuximab against competing standard alternatives, such as carboplatin and paclitaxel combination therapy, with new trials under development. In addition, ongoing trials continue to test novel therapeutic agents in conjunction with radiotherapy as an alternative to radiation with cetuximab.

Reference:

Mell, Loren K 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, The Lancet Oncology,DOI:10.1016/S1470-2045(24)00507-2.