Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients Journal Article
| Authors: | Brahmer, J. R.; Long, G. V.; Hamid, O.; Garon, E. B.; Herbst, R. S.; Andre, T.; Armand, P.; Bajorin, D.; Bellmunt, J.; Burtness, B.; Choueiri, T. K.; Cohen, E. E. W.; Diaz, L. A. Jr; Shitara, K.; Kulkarni, G.; McDermott, D.; Shah, M.; Tabernero, J.; Vogel, A.; Zinzani, P. L.; Jafari, N.; Bird, S.; Snyder, E.; Gause, C.; Bracco, O. L.; Pietanza, M. C.; Gruber, T.; Ribas, A. |
| Article Title: | Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients |
| Abstract: | 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. © 2024 The Authors |
| Keywords: | adolescent; adult; controlled study; aged; major clinical study; prednisone; constipation; fatigue; hepatitis; advanced cancer; diarrhea; drug safety; drug withdrawal; liver cell carcinoma; monotherapy; side effect; treatment duration; skin manifestation; drug megadose; neoplasms; colorectal cancer; cancer immunotherapy; low drug dose; melanoma; drug eruption; anemia; nausea; vomiting; steroid; bladder cancer; renal cell carcinoma; abdominal pain; arthralgia; asthenia; backache; coughing; drug fever; dyspnea; pneumonia; pruritus; drug induced headache; death; microsatellite instability; arthritis; population; uterine cervix cancer; pancreatitis; stomach cancer; colitis; merkel cell carcinoma; safety; phase 3 clinical trial; hyperthyroidism; hypothyroidism; encephalitis; insulin dependent diabetes mellitus; esophagus cancer; sarcoidosis; adverse drug reaction; therapy; small cell lung cancer; classical hodgkin lymphoma; hypoparathyroidism; uveitis; programmed death 1 receptor; non small cell lung cancer; adrenal insufficiency; head and neck squamous cell carcinoma; clinical trial (topic); decreased appetite; optic neuritis; hypophysitis; myositis; vasculitis; thyroiditis; guillain barre syndrome; corticosteroid therapy; myelitis; nephritis; diffuse large b cell lymphoma; myocarditis; human; male; female; article; pembrolizumab; programmed cell death 1 receptor; neuromuscular junction disorder; squamous cell skin carcinoma; tumor mutational burden |
| Journal Title: | European Journal of Cancer |
| Volume: | 199 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-03-01 |
| Start Page: | 113530 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2024.113530 |
| PUBMED: | 38295556 |
| PROVIDER: | scopus |
| PMCID: | PMC11227881 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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