Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients

Abstract

Neoplasms; Pembrolizumab; Safety

Neoplàsies; Pembrolizumab; Seguretat

Neoplasias; Pembrolizumab; Seguridad

Background Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for melanoma or non-small cell lung cancer. Here, we evaluated the safety of pembrolizumab in a broader population of patients from 31 advanced cancer clinical trials across 19 cancer types. Methods Safety was analyzed in patients who received at least one dose of pembrolizumab (200 mg every 3 weeks [Q3W], 10 mg/kg Q2W or Q3W, or 2 mg/kg Q3W). Adverse events (AEs) and immune-mediated AEs and infusion reactions were evaluated. Results Safety data from 8937 patients in 31 trials of pembrolizumab monotherapy were pooled (median, seven administrations; range, 1−59). Median duration on treatment was 4.1 months (range, 0.03−40.1). AEs occurred in 96.6% of patients. Grade 3−5 AEs occurred in 50.6% of patients. AEs led to pembrolizumab discontinuation in 12.7% of patients and death in 5.9%. Immune-mediated AEs and infusion reactions occurred in 23.7% of patients (4.6% experienced multiple immune-mediated AEs/infusion reactions) and led to pembrolizumab discontinuation in 3.6% and death in 0.2%. Grade 3−5 immune-mediated AEs occurred in 6.3% of patients. Serious immune-mediated AEs and infusion reactions occurred in 6.0% of patients. Median time to immune-mediated AE onset was 85 days (range, 13–163). Of 2657 immune-mediated AEs, 22.3% were initially treated with prednisone ≥ 40 mg/day or equivalent, and 8.3% were initially treated with lower steroid doses. Conclusions This pooled analysis of 31 clinical trials showed that pembrolizumab has a consistent safety profile across indications.

Funding for this study was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD). The funder participated in study design, data analysis and interpretation, and manuscript writing. This work was also supported by a grant from the National Cancer Institute, USA Kidney SPORE (5P50CA101942).