Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma

被引：66

作者：

Robert, Caroline ^{[1
,2
]}

Hwu, Wen-Jen ^{[3
]}

Hamid, Omid ^{[4
]}

Ribas, Antoni ^{[5
,6
]}

Weber, Jeffrey S. ^{[7
]}

Daud, Adil, I ^{[8
]}

Hodi, F. Stephen ^{[9
,10
]}

Wolchok, Jedd D. ^{[11
]}

Mitchell , Tara C. ^{[12
]}

Hersey, Peter ^{[13
,14
,15
]}

Dronca, Roxana ^{[16
]}

Joseph, Richard W. ^{[17
]}

Boutros, Celine ^{[1
]}

Min, Le ^{[18
]}

Long, Georgina, V ^{[15
,19
,20
,21
]}

Schachter, Jacob ^{[22
]}

Puzanov, Igor ^{[23
]}

Dummer, Reinhard ^{[24
]}

Lin, Jianxin ^{[25
]}

Ibrahim, Nageatte ^{[25
]}

Diede, Scott J. ^{[25
]}

Carlino, Matteo S. ^{[13
,15
,26
,27
]}

Joshua, Anthony M. ^{[15
,28
,29
,30
]}

机构：

[1] Gustave Roussy, Dept Oncol, Serv Dermatol, Inst Cancerol Gustave Roussy, 114 Rue Edouard Vaillant, F-94805 Villejuif, France

[2] Paris Saclay Univ, CNRS, UMR 3348, Orsay, France

[3] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[4] Angeles Clin & Res Inst, Dept Hematol Oncol, Cedars Sinai Affiliate, 11800 Wilshire Blvd Suite 300, Los Angeles, CA 90025 USA

[5] Univ Calif Los Angeles UCLA, Dept Med, 11-934 Factor Bldg, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles UCLA, Jonsson Comprehens Canc Ctr, 11-934 Factor Bldg, Los Angeles, CA 90095 USA

[7] NYU Langone Hlth, Dept Med, Laura & Isaac Perlmutter Canc Ctr, 522 First Ave,1310 Smilow Bldg, New York, NY 10016 USA

[8] Univ Calif San Francisco, Dept Med, 1600 Divisadero St, San Francisco, CA 94158 USA

[9] Dana Farber Canc Inst, Melanoma Ctr, 450 Brookline Ave, Boston, MA 02215 USA

[10] Dana Farber Canc Inst, Ctr Immunooncol, 450 Brookline Ave, Boston, MA 02215 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA

[12] Univ Penn, Abramson Canc Ctr, Div Hematol & Oncol, 3400 Civ Ctr Blvd South Pavil,Flr 10, Philadelphia, PA 19104 USA

[13] Univ Sydney, Dept Med, Camperdown, NSW 2006, Australia

[14] Centenary Inst, Misendon Rd,Bldg 93, Camperdown, NSW 2050, Australia

[15] Univ Sydney, Melanoma Inst Australia, 40 Rocklands Rd, Wollstonecraft, NSW 2065, Australia

[16] Mayo Clin, Dept Hematol Oncol, 200 1st St SW, Rochester, MN 55905 USA

[17] Mayo Clin, Div Canc Med, Canc Ctr Florida, 4500 San Pablo Rd, Jacksonville, FL 32224 USA

[18] Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA

[19] Royal North Shore Hosp, Reserve Rd, St Leonards, NSW 2065, Australia

[20] Mater Hosp, Wollstonecraft, NSW 2065, Australia

[21] Univ Sydney, Fac Med & Hlth, Sydney, NSW 2006, Australia

[22] Tel HaShomer Hosp, Sheba Med Ctr, Canc Ctr, Div Oncol, Level 2,Emek HaEla St 1, IL-52621 Ramat Gan, Israel

[23] Roswell Pk Comprehens Canc Ctr, Melanoma Sect, Dept Med, 915 CSC Bldg,Elm Carlton St, Buffalo, NY 14263 USA

[24] Univ Zurich, Univ Hosp Zurich, Dept Dermatol, Rdmistr 100, CH-8091 Zurich, Switzerland

[25] Merck & Co Inc, Dept Clin Oncol, 2000 Galloping Hill Rd, Kenilworth, NJ 07033 USA

[26] Westmead Hosp, Dept Med Oncol, Crown Princess Mary Canc Ctr, 12 Moris Rd, Westmead, NSW 2145, Australia

[27] Blacktown Hosp, 18 Blacktown Rd, Blacktown, NSW 2148, Australia

[28] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Oncol, 610 Univ Ave, Toronto, ON M5G 2C1, Canada

[29] St Vincents Hosp, Kinghorn Canc Ctr, 370 Victoria St, Darlinghurst, NSW 2010, Australia

[30] UNSW Sydney, St Vincents Clin Sch, Victoria St, Darlinghurst, NSW 2010, Australia

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 144卷

关键词：

Pembrolizumab; Advanced melanoma; Immune-related adverse events; Immune-checkpoint inhibitors; PD-1; inhibitors; Immunomodulating drugs; Corticosteroid use; INVESTIGATOR-CHOICE CHEMOTHERAPY; ADVERSE EVENTS; IPILIMUMAB; SURVIVAL; ASSOCIATION; NIVOLUMAB;

D O I：

10.1016/j.ejca.2020.11.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objective: Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. Patients and methods: Analysis involved patients who received >= 1 pembrolizumab dose. Leadtime bias was addressed via landmark analyses in patients who were progression-free before day 147. Results: Adverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did (n=79) versus did not (nZ384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months ( p=0.1104). Patients who did (n=17) versus did not (n=62) receive systemic corticosteroids had similar ORRs(70.6% vs. 62.9%) and median TTR(6.4 vs. 5.6months) butnumerically shortermedianPFS(9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both. Conclusions: These results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use. (C) 2020 The Author(s). Published by Elsevier Ltd.

引用

页码：182 / 191

页数：10

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