A new study using data from the FDA Adverse Event Reporting System (FAERS) has shed light on the safety profile of pembrolizumab, particularly when combined with lenvatinib, for patients suffering from hepatocellular carcinoma (HCC). This combination therapy is acknowledged as having significant therapeutic potential for advanced unresectable HCC, but concerns persist over the reporting of adverse drug reactions (ADRs).
Researchers extracted and analyzed adverse event data from HCC patients treated with pembrolizumab alone and those receiving the combo with lenvatinib between January 2014 and December 2023. They identified 459 adverse events (AEs) associated with pembrolizumab monotherapy and 358 for the combination therapy during this extensive period.
Through rigorous statistical analysis employing methods such as the Reporting Odds Ratio (ROR) and Bayesian confidence propagation neural networks (BCPNN), the study established comprehensive insights. Significantly, the evaluation indicated high incidences of gastrointestinal disorders and hepatobiliary abnormalities linked to these therapies.
Among the most frequently reported AEs were hepatic encephalopathy, elevated bilirubin levels, and diarrhea, underscoring the substantial risk profile associated with pembrolizumab treatment. Notably, unexpected serious AEs like dehydration, skin ulcers, and intestinal perforation emerged from the reports, warranting urgent clinical awareness.
The research highlighted the predominant demographics for AE reports, with 80% of incidents occurring among male patients, primarily aged 60 to 74. The findings also revealed varying incidences of AEs geographically, with the United States, China, France, and Japan leading the reports.
Considering the overall serious outcomes reported—579 for pembrolizumab and 450 for the combination with lenvatinib—healthcare practitioners are urged to maintain vigilant monitoring of patients receiving these therapies. The median time to onset of AEs for monotherapy was approximately 80.5 days, compared to 77.5 days for the combination therapy.
Several particularly alarming findings were discussed, including the strong association of pembrolizumab with immune-mediated hepatitis and hepatic dysfunction. The combination therapy seemed to exacerbate these complications, necessitating closer safety surveillance, especially for elderly patients.
This analysis of real-world data seeking to understand the ADRs associated with pembrolizumab and lenvatinib treatment echoes concerns about the need for judicious management approaches to improve patient outcomes.
Future directions call for multicenter trials and cohort studies aimed at validating these insights and establishing clearer management protocols to administer pembrolizumab safely and effectively.