In a phase II trial (Alliance A091802) reported in the Journal of Clinical Oncology, Zandberg et al investigated the survival benefit of adding cetuximab to avelumab in patients with advanced cutaneous squamous cell carcinoma.
Study Details
In the U.S. multicenter trial, 57 evaluable patients were randomly assigned between May 2019 and August 2023 to receive avelumab at 800 mg every 2 weeks plus cetuximab at 500 mg/m2 every 2 weeks (n = 29) or avelumab alone once every 2 weeks for up to 2 years (n = 28); cetuximab was given for 1 year in the avelumab/cetuximab group. Patients had distant metastatic or unresectable locally advanced cutaneous squamous cell carcinoma, were PD-1/PD-L1 inhibitor naive, and had no previous cetuximab in the advanced setting. Crossover to avelumab/cetuximab at progression was permitted. The primary endpoint was progression-free survival.
Key Findings
Median progression-free survival was 11.1 months (95% confidence interval [CI] = 7.6 months to not reached) in the avelumab/cetuximab group vs 3.0 months (95% CI = 2.7–13.6 months) in the avelumab monotherapy group (hazard ratio [HR] = 0.48, 95% CI = 0.23–0.97, P = .018).
A total of nine patients in the avelumab monotherapy group crossed over to receive cetuximab/avelumab at progression. Median progression-free survival–2 in these patients was 11.3 months (95% CI = 5.8 months to not reached); median progression-free survival in these patients prior to crossover was 2.8 months (95% CI = 2.7 months to not reached).
Objective response rates were 27.6% in the avelumab/cetuximab group and 21.4% in the avelumab monotherapy group, with median duration of response not being reached in either group. At a median follow-up of 34.6 months, median overall survival in the avelumab/cetuximab group was not reached (95% CI = 25.2 months to not reached).
Grade ≥ 3 treatment-related adverse events occurred in 48.3% of the avelumab/cetuximab group vs 21.5% of the avelumab monotherapy group; the most common were infusion reaction (20.7%) and acneiform rash (20.7%) in the avelumab/cetuximab group and transaminase elevation (7.1%) in the avelumab monotherapy group. No grade 4 or 5 treatment-related adverse events were observed in the avelumab/cetuximab group; one grade 4 event (glucose intolerance) was observed in the avelumab monotherapy group.
The investigators concluded: “Avelumab [plus] cetuximab significantly improved [progression-free survival] versus avelumab alone in patients with advanced [cutaneous squamous cell carcinoma]. Alliance A091802 supports a larger confirmatory study with the combination of cetuximab and PD-1:PD-(L)1 blockade.”
Dan P. Zandberg, MD, of UPMC Hillman Cancer Center, University of Pittsburgh, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of all study authors, visit the ascopubs.org.
