A recent phase 2/3 clinical trial, NRG-HN004, has revealed that durvalumab, an immunotherapy drug, does not improve outcomes compared to cetuximab, a targeted therapy, in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) who have contraindications to cisplatin. The study, published in The Lancet Oncology, highlights the ongoing challenges in finding effective treatments for patients unable to tolerate cisplatin, a standard chemotherapy drug for this cancer type.
The trial enrolled 190 patients with stage III to IVB HNSCC who were ineligible for cisplatin due to factors such as hearing impairment, renal impairment, or poor performance status. Patients were randomized to receive either durvalumab or cetuximab in combination with radiotherapy. The primary endpoint was progression-free survival (PFS).
Trial Results
The results indicated that cetuximab outperformed durvalumab. At a median follow-up of 2.3 years, the 2-year PFS was 50.6% in the durvalumab group and 63.7% in the cetuximab group. The trial was halted early based on an interim futility analysis that suggested durvalumab was unlikely to demonstrate superior efficacy.
According to lead study author Dr. Loren K. Mell, a radiation oncologist at the University of California San Diego Health, "Our results support the idea that radiation with cetuximab is a very good alternative for patients who cannot get standard cisplatin."
Safety and Tolerability
The safety profiles of the two treatments were comparable, with similar rates of grade 3 or 4 adverse events. The most common severe side effects included dysphagia, lymphopenia, and oral mucositis. However, deaths from treatment-related adverse events were more frequent in the durvalumab group (9%) compared to the cetuximab group (2%).
Implications for Clinical Practice
The findings from this trial provide clarity for clinicians treating HNSCC patients who cannot receive cisplatin. Cetuximab remains a reasonable alternative in this setting. Experts suggest that future trials should consider cetuximab as a comparator arm when evaluating new therapies for this patient population.
Dr. Charalampos Floudas of NCI’s Center for Cancer Research noted that these findings align with other recent trials, such as those involving pembrolizumab, suggesting that immunotherapy with radiation may not be as effective as targeted therapy for many head and neck cancer patients.
Future Directions
Ongoing research is focused on identifying specific subgroups of patients who may benefit from immunotherapy in combination with radiation. Clinical trials are also exploring novel treatment sequences, such as administering immunotherapy after chemotherapy and radiation, which has shown promise in other cancer types like lung cancer.
