Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial

被引:111
作者
Hughes, B. G. M. [1 ,2 ]
Munoz-Couselo, E. [3 ,4 ]
Mortier, L. [5 ]
Bratland, A. [6 ]
Gutzmer, R. [7 ,8 ]
Roshdy, O. [9 ]
Mendoza, R. Gonzalez [10 ]
Schachter, J. [11 ]
Arance, A. [12 ]
Grange, F. [13 ,14 ]
Meyer, N. [15 ,16 ]
Joshi, A. [17 ]
Billan, S. [18 ]
Zhang, P. [19 ]
Gumuscu, B. [19 ]
Swaby, R. F. [19 ]
Grob, J. -j. [20 ]
机构
[1] Royal Brisbane & Womens Hosp, Canc Care Serv, Herston, Qld, Australia
[2] Univ Queensland, Brisbane, Qld, Australia
[3] Hosp Valle De Hebron, Barcelona, Spain
[4] Vall dHebron Inst Oncol, Barcelona, Spain
[5] Univ Lille, CHU Lille, INSERM, U1189, Lille, France
[6] Oslo Univ Sykehus, Oslo, Norway
[7] Hannover Med Sch, Skin Canc Ctr Hannover, Dept Dermatol & Allergy, Hannover, Germany
[8] Ruhr Univ Bochum Campus Minden, Muhlenkreiskliniken, Minden, Germany
[9] Jewish Gen Hosp, Montreal, PQ, Canada
[10] Ctr Estatal Cancerologiade Chihuahua, Chihuahua, Mexico
[11] Chaim Sheba Med Ctr Tel HaShomer, Ramat Gan, Israel
[12] Hosp Clin Barcelona, Barcelona, Spain
[13] Hop Robert Debre, Ctr Hosp Univ Reims, Dermatol Dept, Reims, France
[14] Ctr Hosp Valence, Dept Dermatol, Valence, France
[15] Inst Univ Canc, Dermatol, Toulouse, France
[16] CHU Toulouse, Toulouse, France
[17] Townsville Univ Hosp, Dept Med Oncol, Townsville, Qld, Australia
[18] Rambam Hlth Care Campus, Dept Oncol, Head & Neck Ctr, Haifa, Israel
[19] Merck & Co Inc, Kenilworth, NJ USA
[20] Aix Marseille Univ, Serv Dermatol & Cancerol Cutanee, Marseille, France
关键词
cutaneous squamous cell carcinoma; programmed cell death protein 1 (PD-1); immunotherapy; pembrolizumab; HEAD;
D O I
10.1016/j.annonc.2021.07.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). Patients and methods: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. Results: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. Conclusions: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.
引用
收藏
页码:1276 / 1285
页数:10
相关论文
共 23 条
[1]   Primary care: Cutaneous squamous-cell carcinoma [J].
Alam, M ;
Ratner, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (13) :975-983
[2]   Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study [J].
Burtness, Barbara ;
Harrington, Kevin J. ;
Greil, Richard ;
Soulieres, Denis ;
Tahara, Makoto ;
de Castro, Gilberto, Jr. ;
Psyrri, Amanda ;
Baste, Neus ;
Neupane, Prakash ;
Bratland, Ase ;
Fuereder, Thorsten ;
Hughes, Brett G. M. ;
Mesia, Ricard ;
Ngamphaiboon, Nuttapong ;
Rordorf, Tamara ;
Ishak, Wan Zamaniah Wan ;
Hong, Ruey-Long ;
Mendoza, Rene Gonzalez ;
Roy, Ananya ;
Zhang, Yayan ;
Gumuscu, Burak ;
Cheng, Jonathan D. ;
Jin, Fan ;
Rischin, Danny .
LANCET, 2019, 394 (10212) :1915-1928
[3]   Cutaneous Squamous Cell Carcinoma: A Review of High-Risk and Metastatic Disease [J].
Burton, Kyle A. ;
Ashack, Kurt A. ;
Khachemoune, Amor .
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY, 2016, 17 (05) :491-508
[4]   Cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma (mCSCC): Preliminary safety and efficacy results from a phase I clinical trial [J].
Clingan, P. ;
Brungs, D. ;
Ladwa, R. ;
Mant, A. M. ;
McGrath, M. ;
Tazbirkova, A. ;
Koralewski, P. ;
Lugowska, I. ;
Charoentum, C. ;
Dechaphunkul, A. ;
Sriuranpong, V. ;
Oliviero, J. ;
Harris, D. L. .
ANNALS OF ONCOLOGY, 2020, 31 :S736-S736
[5]   Management of High-Risk Squamous Cell Carcinoma of the Skin [J].
Fu, Teresa ;
Aasi, Sumaira Z. ;
Hollmig, S. Tyler .
CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2016, 17 (07)
[6]   Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629) [J].
Grob, Jean-Jacques ;
Gonzalez, Rene ;
Basset-Seguin, Nicole ;
Vornicova, Olga ;
Schachter, Jacob ;
Joshi, Abhishek ;
Meyer, Nicolas ;
Grange, Florent ;
Piulats, Josep M. ;
Bauman, Jessica R. ;
Zhang, Pingye ;
Gumuscu, Burak ;
Swaby, Ramona F. ;
Hughes, Brett G. M. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (25) :2916-+
[7]  
Hall Evan T, 2020, Am Soc Clin Oncol Educ Book, V40, P1, DOI 10.1200/EDBK_278953
[8]   COSIBELIMAB, AN ANTI-PD-L1 ANTIBODY: PRELIMINARY SAFETY AND EFFICACY RESULTS FROM A GLOBAL, MULTICOHORT PHASE 1 CLINICAL TRIAL [J].
Harris, Dean ;
Brungs, Daniel ;
Ladwah, Rahul ;
Mant, Andrew ;
McGrath, Margaret ;
Tazbirkova, Andrea ;
Akopov, Andrey ;
Fadeeva, Natalia ;
Kasparov, Boris ;
Kovalenko, Nadezhda ;
Kozlov, Vadim ;
Moiseenko, Fedor ;
Oschepkov, Vasiliy ;
Koralewski, Piotr ;
Kowalski, Dariusz ;
Lugowska, Iwona ;
Charoentumn, Chaiyut ;
Dechaphunkul, Arunee ;
Sriuranpong, Virote ;
Oliviero, James ;
Clingan, Philip .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 :A242-A243
[9]  
KEYTRUDA<(R), 2021, KEYTRUDA PEMBROLIZUM
[10]   Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas [J].
Maubec, Eve ;
Boubaya, Marouane ;
Petrow, Peter ;
Beylot-Barry, Marie ;
Basset-Seguin, Nicole ;
Deschamps, Lydia ;
Grob, Jean-Jacques ;
Dreno, Brigitte ;
Scheer-Senyarich, Isabelle ;
Bloch-Queyrat, Coralie ;
Leccia, Marie-Therese ;
Stefan, Andreea ;
Saiag, Philippe ;
Grange, Florent ;
Meyer, Nicolas ;
de Quatrebarbes, Julie ;
Dinulescu, Monica ;
Legoupil, Delphine ;
Machet, Laurent ;
Dereure, Olivier ;
Zehou, Ouidad ;
Montaudie, Henri ;
Wierzbicka-Hainaut, Ewa ;
Le Corre, Yannick ;
Mansard, Sandrine ;
Guegan, Sarah ;
Arnault, Jean-Philippe ;
Dalac, Sophie ;
Aubin, Francois ;
Alloux, Celine ;
Lopez, Isabelle ;
Cherbal, Soufian ;
Tibi, Annick ;
Levy, Vincent .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (26) :3051-3061