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

被引:17
作者
Brahmer, Julie R. [1 ,26 ]
Long, Georgina, V [2 ,3 ]
Hamid, Omid [4 ]
Garon, Edward B. [5 ]
Herbst, Roy S. [6 ]
Andre, Thierry [7 ,8 ]
Armand, Philippe [9 ]
Bajorin, Dean [10 ]
Bellmunt, Joaquim [11 ,12 ]
Burtness, Barbara [6 ]
Choueiri, Toni K. [13 ]
Cohen, Ezra E. W. [14 ]
Diaz Jr, Luis A. [10 ]
Shitara, Kohei [15 ]
Kulkarni, Girish [16 ]
McDermott, David [17 ]
Shah, Manish [18 ]
Tabernero, Josep [19 ,20 ]
Vogel, Arndt [21 ,22 ,23 ]
Zinzani, Pier Luigi [24 ]
Jafari, Niusha [25 ]
Birdu, Steven [25 ]
Snyderu, Ellen [25 ]
Gause, Christine [25 ]
Braccou, Oswaldo L. [25 ]
Pietanza, M. Catherine [25 ]
Gruberu, Todd [25 ]
Ribas, Antoni [5 ]
机构
[1] Johns Hopkins Kimmel Canc Ctr, 1800 Orleans St, Baltimore, MD 21287 USA
[2] Univ Sydney, Melanoma Inst Australia, 40 Rocklands Rd North Sydney, Sydney, NSW 2060, Australia
[3] Royal North Shore & Mater Hosp, 40 Rocklands Rd North Sydney, Sydney, NSW 2060, Australia
[4] Cedars Sinai Angeles Clinic & Res Inst, 11800 Wilshire Blvd 300, Los Angeles, CA 90025 USA
[5] UCLA, David Geffen Sch Med, 2825 Santa Monica Blvd,Suite 200, Santa Monica, CA 90404 USA
[6] Yale Sch Med, 333 Cedar St, New Haven, CT 06510 USA
[7] Sorbonne Univ, 184 Rue Faubourg St Antoine, F-75012 Paris, France
[8] Hop St Antoine, 184 Rue Faubourg St Antoine, F-75012 Paris, France
[9] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA
[10] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA
[11] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA
[12] IMIM Lab, 450 Brookline Ave, Boston, MA 02115 USA
[13] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA
[14] UC San Diego Hlth, Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92037 USA
[15] Natl Canc Ctr Hosp East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan
[16] Univ Hlth Network, Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON MG5 2C4, Canada
[17] Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA
[18] Weill Cornell Med, 1300 York Ave, New York, NY 10065 USA
[19] Vall dHebron Hosp Campus, Pg Vall dHebron 119, Barcelona 08035, Spain
[20] Inst Oncol VHIO, Pg Vall dHebron 119, Barcelona 08035, Spain
[21] Toronto Gen Hosp, Div Gastroenterol & Hepatol, Toronto, ON, Canada
[22] Princess Margaret Canc Ctr, Med Oncol, Toronto, ON, Canada
[23] Hannover Med Sch, Hannover, Germany
[24] Univ Bologna, IRCCS Azienda Ospedaliero, Dipartimento Sci Med & Chirurg, Ist Ematol Seragnoli, Bologna, Italy
[25] Merck & Co Inc, Rahway, NJ USA
[26] Johns Hopkins Kimmel Canc Ctr, 401 N Broadway, Baltimore, MD 21231 USA
关键词
Safety; Pembrolizumab; Programmed cell death 1 receptor; Neoplasms;
D O I
10.1016/j.ejca.2024.113530
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 7 条
[1]  
[Anonymous], 2023, KEYTRUDA (pembrolizumab) [package insert]
[2]  
Dohme B.V., 2023, KEYTRUDA 25 mg/mL concentrate for solution for infusion (SPC)
[3]   Original Research Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy [J].
Ghisoni, E. ;
Wicky, A. ;
Bouchaab, H. ;
Imbimbo, M. ;
Delyon, J. ;
Moura, B. Gautron ;
Gerard, C. L. ;
Latifyan, S. ;
Ozdemir, B. C. ;
Caikovski, M. ;
Pradervand, S. ;
Tavazzi, E. ;
Gatta, R. ;
Marandino, L. ;
Valabrega, G. ;
Aglietta, M. ;
Obeid, M. ;
Homicsko, K. ;
Alfonso, N. N. Mederos ;
Zimmermann, S. ;
Coukos, G. ;
Peters, S. ;
Cuendet, M. A. ;
Di Maio, M. ;
Michielin, O. .
EUROPEAN JOURNAL OF CANCER, 2021, 149 :153-164
[4]   Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up [J].
Haanen, J. ;
Obeid, M. ;
Spain, L. ;
Carbonnel, F. ;
Wang, Y. ;
Robert, C. ;
Lyon, A. R. ;
Wick, W. ;
Kostine, M. ;
Peters, S. ;
Jordan, K. ;
Larkin, J. .
ANNALS OF ONCOLOGY, 2022, 33 (12) :1217-1238
[5]   Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma [J].
Robert, Caroline ;
Hwu, Wen-Jen ;
Hamid, Omid ;
Ribas, Antoni ;
Weber, Jeffrey S. ;
Daud, Adil, I ;
Hodi, F. Stephen ;
Wolchok, Jedd D. ;
Mitchell , Tara C. ;
Hersey, Peter ;
Dronca, Roxana ;
Joseph, Richard W. ;
Boutros, Celine ;
Min, Le ;
Long, Georgina, V ;
Schachter, Jacob ;
Puzanov, Igor ;
Dummer, Reinhard ;
Lin, Jianxin ;
Ibrahim, Nageatte ;
Diede, Scott J. ;
Carlino, Matteo S. ;
Joshua, Anthony M. .
EUROPEAN JOURNAL OF CANCER, 2021, 144 :182-191
[6]   Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update [J].
Schneider, Bryan J. ;
Naidoo, Jarushka ;
Santomasso, Bianca D. ;
Lacchetti, Christina ;
Adkins, Sherry ;
Anadkat, Milan ;
Atkins, Michael B. ;
Brassil, Kelly J. ;
Caterino, Jeffrey M. ;
Chau, Ian ;
Davies, Marianne J. ;
Ernstoff, Marc S. ;
Fecher, Leslie ;
Ghosh, Monalisa ;
Jaiyesimi, Ishmael ;
Mammen, Jennifer S. ;
Naing, Aung ;
Nastoupil, Loretta J. ;
Phillips, Tanyanika ;
Porter, Laura D. ;
Reichner, Cristina A. ;
Seigel, Carole ;
Song, Jung-Min ;
Spira, Alexander ;
Suarez-Almazor, Maria ;
Swami, Umang ;
Thompson, John A. ;
Vikas, Praveen ;
Wang, Yinghong ;
Weber, Jeffrey S. ;
Funchain, Pauline ;
Bollin, Kathryn .
JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (36) :4073-+
[7]   Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis [J].
Wang, Peng-Fei ;
Chen, Yang ;
Song, Si-Ying ;
Wang, Ting-Jian ;
Ji, Wen-Jun ;
Li, Shou-Wei ;
Liu, Ning ;
Yan, Chang-Xiang .
FRONTIERS IN PHARMACOLOGY, 2017, 8