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

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 199卷

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.

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