REAL-WORLD SAFETY PROFILE OF PEMBROLIZUMAB VS. NIVOLUMAB AND CETUXIMAB IN ADULTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA: A COMPARATIVE ANALYSIS

Author(s)

Saba Dangpiaei, MBA, PharmD1, Adrienne Duckworth, AOCNP2, Khalid K. Kamal, PhD2, Sabina O. Nduaguba, PhD2;
1West Virginia University, Ph.D. Student, Morgantown, WV, USA, 2West Virginia University, Morgantown, WV, USA
OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) remains a major cause of morbidity and mortality in the U.S., largely driven by tobacco, alcohol, and human papillomavirus (HPV) infection. Immunotherapy, particularly pembrolizumab, has replaced cetuximab-based chemotherapy as first-line treatment for recurrent or metastatic disease but introduces immune-related adverse events, including pneumonitis, mucositis, thyroid dysfunction, anemia, and neutropenia. However, real-world comparative safety data across HNSCC treatments remain limited. This study aimed to compare the risk of immune-related adverse events associated with pembrolizumab, as the reference group, versus nivolumab and cetuximab among HNSCC patients.
METHODS: Using retrospective electronic health record data from TriNetX, we compared adverse event risks between pembrolizumab and nivolumab or cetuximab after propensity score matching on biological and comorbidity factors. Risk estimates included hazard ratios (HRs) and odds ratios (ORs). Time-to-event outcomes were assessed using Kaplan-Meier curves with log-rank tests.
RESULTS: After matching, 3,518 patients were included in the pembrolizumab-nivolumab comparison and 4,107 in the pembrolizumab-cetuximab comparison. Compared with nivolumab, pembrolizumab was associated with higher risk of pneumonitis (HR = 1.11 [1.01-1.22], p = 0.030), oral mucositis (HR = 1.29 [1.11-1.49], p = 0.001), hemolytic anemia (HR = 1.28 [1.13-1.44], p < 0.001), and neutropenia (HR = 1.54 [1.33-1.78], p < 0.001), while hyperthyroidism risk was lower (HR = 0.74 [0.61-0.89], p = 0.002). Compared with cetuximab, pembrolizumab showed lower hazard of oral mucositis (HR = 0.32 [0.29-0.37], p < 0.001) but higher hazards of hypothyroidism (HR = 1.50 [1.34-1.67], p < 0.001), hyperthyroidism (HR = 2.47 [1.90-3.22], p < 0.001), and hemolytic anemia (HR = 1.66 [1.46-1.89], p < 0.001).
CONCLUSIONS: Pembrolizumab was associated with higher risks of hematologic and thyroid adverse events than cetuximab but lower oral mucositis. Compared with nivolumab, it showed higher risks of mucositis and anemia but lower hyperthyroidism, which may inform treatment selection based on toxicity risk.

Conference/Value in Health Info

2026-05, ISPOR 2026, Philadelphia, PA, USA

Value in Health, Volume 29, Issue S6

Code

P55

Topic

Epidemiology & Public Health

Topic Subcategory

Safety & Pharmacoepidemiology

Disease

SDC: Oncology

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