Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy

PURPOSE Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited. METHODS We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI. We extracted objective response rate (ORR), duration of treatment (DOT), and overall survival (OS) and compared them on the basis of patient characteristics. Multivariable models assessed associations between patient and tumor characteristics and outcomes. RESULTS We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC. Overall, the ORR was 21.4%, the median DOT was 1.9 months, and the median OS was 6.3 months. Patients receiving cetuximab with chemotherapy had a higher ORR (27.7% v 8.7%) and longer median DOT but similar OS compared with monotherapy. Virus-independent HNSCC had higher ORR (28.6% v 10.7%), longer DOT (3.3 v 1.2 months; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.90]), and longer OS (8.1 v 4.6 months; HR, 0.40 [95% CI, 0.19 to 0.83]). In multivariable models, virus-independent disease and negative smoking history were associated with improved OS. Concurrent chemotherapy, age, and sex were not associated with differences in OS. When assessing genomic data, TP53 mutations were associated with improved DOT (HR, 0.33 [95% CI, 0.15 to 0.70]) and OS (HR, 0.38 [95% CI, 0.17 to 0.86]). CONCLUSION Cetuximab-based therapy shows limited efficacy in R/M HNSCC post-ICI, although outcomes were better in virus-independent HNSCC and nonsmokers. The findings may improve prognostication and patient selection for cetuximab after ICI in R/M HNSCC.