Cetuximab-Related Skin Toxicity as a Prognostic Marker in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Retrospective Analysis of the EXTREME Regimen

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Fidan M. C., Safarov S., Abbasov H., Aliyev V., Çerme E., Alan Ö., ...Daha Fazla

Cerrahpaşa Medical Journal, cilt.20, sa.8, ss.1-9, 2026 (TRDizin)

Özet

Objective: Cetuximab-induced skin toxicity has been proposed as a predictive biomarker of treatment efficacy in cetuximab-based regimens. However, its prognostic significance in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with the EXTREME regimen remains limited. This study investigated the impact of cetuximab-related skin toxicity on progression-free survival (PFS) and overall survival (OS) in R/M HNSCC.Methods: This single-center, retrospective cohort study included 79 patients with histopathologically con-firmed unresectable locally advanced or metastatic HNSCC who received first-line platinum-based chemo-therapy with 5-fluorouracil (5-FU) and cetuximab (EXTREME regimen) between June 2014 and July 2024. Patients were stratified by the presence or absence of cetuximab-related skin toxicity. Toxicities were graded per National Cancer Institute Common Terminology Criteria for Adverse Events NCI-CTCAE v5.0. Survival analyses were performed using the Kaplan–Meier method and Cox proportional hazards regression.Results: Median age was 63 years (range 34-87), and 75.9% were male. Cetuximab-related skin toxicity was observed in 27 patients (34.2%), and was the most frequent toxicity type, followed by diarrhea (17.0%) and hypomagnesemia (13.2%). Patients with skin toxicity had significantly longer OS (14.1 vs. 10.1 months; HR: 0.545; 95% CI: 0.325-0.916; P = .022). No significant difference was observed in PFS (6.3 vs. 5.2 months; HR: 0.91; 95% CI: 0.57-1.47; P = .715). On multivariate analysis, skin toxicity was independently associ-ated with improved OS (HR: 0.545; 95% CI: 0.325-0.916; P = .022). Eastern Cooperative Oncology Group (ECOG) ≥2 was an independent adverse prognostic factor for both PFS (HR: 3.084; 95% CI: 1.578-6.028; P< .001) and OS (HR: 6.419; 95% CI: 3.140-13.121; P < .001).Conclusion: Cetuximab-induced skin toxicity was independently associated with improved OS in R/M HNSCC patients treated with the EXTREME regimen, suggesting its potential role as a pharmacodynamic biomarker of cetuximab efficacy. Prospective studies incorporating molecular biomarkers are warranted.