Durvalumab Is Not Superior to Cetuximab in Head, Neck Cancer

TOPLINE: 

Compared with cetuximab with concurrent radiotherapy, adjuvant durvalumab alongside radiotherapy did not enhance outcomes in patients with head and neck squamous cell carcinoma (HNSCC) who are ineligible for cisplatin.

METHODOLOGY:

• Although cisplatin with concurrent radiotherapy is the standard treatment for advanced HNSCC, cisplatin is contraindicated in many patients. Optimal management of patients considered unfit for cisplatin remains controversial, with no clear alternate standard of care.
• To compare cetuximab and durvalumab as an alternate to cisplatin, researchers conducted a multicenter phase 2/3 trial in which 186 patients with locoregionally advanced HNSCC and contraindications to cisplatin were randomly assigned in a 2:1 ratio to receive radiotherapy concurrently with either durvalumab (n = 123) or cetuximab (n = 63).
• Participants (median age, 72 years; 83% White) received intensity-modulated radiotherapy (70 Gy in 35 daily fractions over 7 weeks) with either 1500-mg intravenous durvalumab every 4 weeks for seven cycles or 400-mg/m² intravenous cetuximab initially then 250 mg/m² weekly for eight cycles.
• Phase 2 accrual for the trial was suspended in late July 2021, after an interim futility analysis, and was permanently closed in September 2022.
• The primary endpoint for phase 2 was progression-free survival, with overall survival as the intended primary endpoint for phase 3.

TAKEAWAY:

• At a median follow-up of 2.3 years, the 2-year progression-free survival rate was lower in the durvalumab group but not significantly so: 50.6% vs 63.7% in the cetuximab group (hazard ratio [HR], 1.33; 95% CI, 0.84-2.12; P = .89). The median progression-free survival was 2.2 years with durvalumab and 2.7 years with cetuximab (adjusted HR, 1.43; 95% CI, 0.84-2.45).
• In post hoc follow-up, the 2-year overall survival rates were 69.3% in the durvalumab group vs 77.5% in the cetuximab group. The median overall survival was not reached in either group (HR,1.30; 95% CI, 0.74-2.28).
• Adverse events were similar between the groups. 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%, respectively), and oral mucositis (11% vs 18%).
• Treatment-related serious adverse events were reported in 24% of patients receiving durvalumab and 25% of those receiving cetuximab, with treatment-related deaths occurring in 3% of the durvalumab group (four patients) and 2% of the cetuximab group (one patient).

IN PRACTICE:

“Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin,” the authors concluded. “These findings are consistent with the results of other trials indicating a lack of benefit of immune checkpoint inhibitors compared with cetuximab in patients with HNSCC who are ineligible for cisplatin.”

SOURCE:

The study, led by Loren K. Mell, MD, University of California, San Diego, was published online in The Lancet Oncology.

LIMITATIONS:

Because the study was closed early, robust estimates of treatment effects within subgroups could not be obtained owing to small subsample sizes. Additionally, the impact of p16 status on the effectiveness of checkpoint inhibitors in this population could not be determined.

DISCLOSURES:

The study received funding support from the National Cancer Institute and AstraZeneca. Several authors reported receiving grants and honoraria or having other ties with various sources, including AstraZeneca.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.