Pharmacovigilance Assessment of PD-1 Antibody Therapy in Head and Neck Cancer: Risk Factor Analysis Using FAERS Database.

[PURPOSE] Pembrolizumab and nivolumab, programmed death-1 (PD-1) antibodies, are currently approved for treating head and neck squamous cell carcinoma (HNSCC). This study aimed to identify and characterize adverse events (AEs) associated with these agents and to compare their safety profiles in order to provide clinical guidance.

[METHODS] AEs reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Data for pembrolizumab spanned from Q3 2016 to Q4 2024, while nivolumab data covered Q4 2016 to Q4 2024. We employed the reporting odds ratio (ROR) and proportional reporting ratio (PRR) to evaluate AEs signals associated with pembrolizumab and nivolumab in HNSCC treatment. A signal was defined as meeting the following criteria: a ≥3, ROR 95% confidence interval lower limit >1.0, PRR ≥ 2, χ value ≥4.

[FINDINGS] A total of 1562 AE reports were retrieved from FAERS, with 428 for pembrolizumab and 1134 for nivolumab. Reports for males were more than four times as common as reports for females. As for pembrolizumab and nivolumab, patients aged 65 to 85 and 18 to 64.9 years reported the highest number of AEs. Interestingly, pembrolizumab was associated with 11 unexpected AEs, including pulmonary mass, cirrhosis, and Pneumocystis jirovecii pneumonia, whereas nivolumab was linked to 16 unexpected AEs, such as cardiac failure, device-related infection, and falls. Additionally, sex-based differences and similarities were observed in AE profiles between the two treatments.

[IMPLICATIONS] Providing real-world evidence on the AE profiles of pembrolizumab and nivolumab in patients with HNSCC, our study highlights important sex-based differences and suggests that clinicians should consider potential sex-specific AEs when using these PD-1 inhibitors.