Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group

被引：43

作者：

Hober, Candice ^{[1
]}

Fredeau, Lisa ^{[2
]}

Pham-Ledard, Anne ^{[3
,4
]}

Boubaya, Marouane ^{[2
]}

Herms, Florian ^{[5
]}

Celerier, Philippe ^{[6
]}

Aubin, Francois ^{[7
,8
]}

Beneton, Nathalie ^{[9
]}

Dinulescu, Monica ^{[10
]}

Jannic, Arnaud ^{[11
]}

Meyer, Nicolas ^{[12
,13
]}

Duval-Modeste, Anne-Benedicte ^{[14
]}

Cesaire, Laure ^{[15
]}

Neidhardt, Eve-Marie ^{[16
]}

Archier, Elodie ^{[17
]}

Dreno, Brigitte ^{[18
,19
,20
,21
]}

Lesage, Candice ^{[22
]}

Berthin, Clemence ^{[23
]}

Kramkimel, Nora ^{[24
]}

Grange, Florent ^{[25
,26
]}

de Quatrebarbes, Julie ^{[27
]}

Stoebner, Pierre-Emmanuel ^{[28
,29
]}

Poulalhon, Nicolas ^{[30
]}

Arnault, Jean-Philippe ^{[31
]}

Abed, Safia ^{[32
]}

Bonniaud, Bertille ^{[33
]}

Darras, Sophie ^{[34
]}

Heidelberger, Valentine ^{[35
]}

Devaux, Suzanne ^{[36
]}

Moncourier, Marie ^{[37
]}

Misery, Laurent ^{[38
,39
]}

Mansard, Sandrine ^{[40
]}

Etienne, Maxime ^{[41
]}

Brunet-Possenti, Florence ^{[42
]}

Jacobzone, Caroline ^{[43
]}

Lesbazeilles, Romain ^{[44
,45
]}

Skowron, Francois ^{[26
,68
]}

Sanchez, Julia ^{[25
,69
]}

Catala, Stephanie ^{[46
]}

Samimi, Mahtab ^{[47
,48
]}

Tazi, Youssef ^{[49
]}

Spaeth, Dominique ^{[50
]}

Gaudy-Marqueste, Caroline ^{[51
,52
]}

Collard, Olivier ^{[53
]}

Triller, Raoul ^{[54
]}

Pracht, Marc ^{[55
]}

Dumas, Marc ^{[56
]}

Peuvrel, Lucie ^{[57
]}

Combe, Pierre ^{[58
]}

Lauche, Olivier ^{[59
]}

机构：

[1] Ctr Hosp Univ CHU Lille, F-59037 Lille, France

[2] Hop Avicenne, AP HP, F-93000 Bobigny, France

[3] CHU Bordeaux, F-33000 Bordeaux, France

[4] Univ Bordeaux, F-33000 Bordeaux, France

[5] Hop St Louis, AP HP, F-75010 Paris, France

[6] CH St Louis La Rochelle, F-17000 La Rochelle, France

[7] Univ Bourgogne Franche Comte, F-25000 Besancon, France

[8] CHU Besancon, F-25000 Besancon, France

[9] CH Mans, F-72037 Le Mans, France

[10] Hop Pontchaillou, F-35000 Rennes, France

[11] Hop Henri Mondor, AP HP, F-94000 Creteil, France

[12] Inst Univ Canc Toulouse, F-31100 Toulouse, France

[13] CHU Toulouse, F-31300 Toulouse, France

[14] Hop Charles Nicolle, F-76038 Rouen, France

[15] Hop Cote Nacre, F-14000 Caen, France

[16] Ctr Leon Berard, F-69008 Lyon, France

[17] Hop St Joseph, F-13008 Marseille, France

[18] CHU Nantes, F-44000 Nantes, France

[19] Univ Nantes, F-44000 Nantes, France

[20] CHU Nantes, Ctr Invest Clin 1413, Inst Natl Sante & Rech Med INSERM, F-44000 Nantes, France

[21] Inst Natl Sante & Rech Med INSERM, Ctr Rech Cancerol & Immunol Nantes Angers CRCINA, F-44007 Nantes, France

[22] CHU Montpellier, F-34295 Montpellier, France

[23] CHU Angers, F-49100 Angers, France

[24] Hop Cochin, AP HP, F-75014 Paris, France

[25] CHU Reims, F-51092 Reims, France

[26] CH Valence, F-26000 Valence, France

[27] CH Annecy Genevois, F-74370 Annecy, France

[28] CHU Nimes, F-30900 Nimes, France

[29] Univ Montpellier I, UMR CNRS 5247, F-34090 Montpellier, France

[30] Hosp Civils Lyon, Hop Lyon Sud, F-69310 Lyon, France

[31] CHU Amiens Picardie, F-80000 Amiens, France

[32] Hop Instruct Armees St Anne, F-83000 Toulon, France

[33] CHU, F Mitterrand Dijon Bourgogne, F-21000 Dijon, France

[34] CH Boulogne Sur Mer, F-62200 Boulogne Sur Mer, France

[35] CH Robert Ballanger, F-93600 Aulnay Sous Bois, France

[36] CH Cote Basque, F-64109 Bayonne, France

[37] CHU Grenoble Alpes, F-38700 Grenoble, France

[38] CHU Brest, F-29200 Brest, France

[39] Univ Bretagne Occidentale, F-29200 Brest, France

[40] CHU Clermont Ferrand, F-63100 Clermont Ferrand, France

[41] CH Intercommunal Quimper, CH Cornouaille, F-29000 Quimper, France

[42] Hop Bichat Claude Bernard, AP HP, F-75018 Paris, France

[43] Hop Scorff, F-56322 Lorient, France

[44] CHU Poitiers, F-86021 Poitiers, France

[45] CH Niort, F-79000 Niort, France

[46] Clin St Pierre, F-66000 Perpignan, France

[47] CH Reg Univ Trousseau Tours, F-37170 Chambray Les Tours, France

[48] Univ Tours, ISP1282 UMR INRA, F-37000 Tours, France

[49] Clin St Anne, F-67000 Strasbourg, France

[50] Ctr Oncol Gentilly, F-54000 Nancy, France

来源：

CANCERS | 2021年 / 13卷 / 14期

关键词：

PD-1-blocking antibody; cemiplimab; cutaneous squamous cell carcinoma; real-life setting; immunocompromised; chronic dermatosis; STEVENS-JOHNSON SYNDROME; TOXIC EPIDERMAL NECROLYSIS; SKIN-CANCER; TRANSPLANT RECIPIENTS; NIVOLUMAB; DEATH; RISK; HEAD; NECK; POPULATION;

D O I：

10.3390/cancers13143547

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Prognosis of advanced cutaneous squamous-cell carcinoma (CSCC) is poor. Recent clinical trials have shown that immunotherapy achieves significantly improved survival of patients with advanced CSCCs. However, few real-world data are available on treatment patterns and clinical outcomes of patients with advanced CSCCs receiving anti-programmed cell-death protein-1 (PD-1). To approach this issue, we conducted a retrospective study on 245 patients with advanced CSCCs from 58 centers who had been enrolled in an early-access program; 240 received cemiplimab. Our objectives were to evaluate, in the real-life setting, best overall response rate, progression-free survival, overall survival and safety. Results demonstrated cemiplimab efficacy in patients with advanced CSCCs, regardless of immune status. Patients with good Eastern Cooperative Oncology Group performance status benefited more from cemiplimab. The safety profile was acceptable. Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) >= 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of >= 1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus >= 2. Multivariate analysis retained PS >= 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS >= 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.

引用

页数：14

共 57 条

[11] Toxic epidermal necrolysis due to anti-PD1 treatment with fatal outcome [J].

Demirtas, S. ;

El Aridi, L. ;

Acquitter, M. ;

Fleuret, C. ;

Plantin, P. .

ANNALES DE DERMATOLOGIE ET DE VENEREOLOGIE, 2017, 144 (01) :65-66

[12] Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An Update [J].

Dodiuk-Gad, Roni P. ;

Chung, Wen-Hung ;

Valeyrie-Allanore, Laurence ;

Shear, Neil H. .

AMERICAN JOURNAL OF CLINICAL DERMATOLOGY, 2015, 16 (06) :475-493

[13] Cutaneous Human Papillomaviruses and Squamous Cell Carcinoma of the Skin: Nested Case-Control Study [J].

Faust, Helena ;

Andersson, Kristin ;

Luostarinen, Tapio ;

Gislefoss, Randi E. ;

Dillner, Joakim .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2016, 25 (04) :721-724

[14] Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States [J].

Garrett, Giorgia L. ;

Blanc, Paul D. ;

Boscardin, John ;

Lloyd, Amanda Abramson ;

Ahmed, Rehana L. ;

Anthony, Tiffany ;

Bibee, Kristin ;

Breithaupt, Andrew ;

Cannon, Jennifer ;

Chen, Amy ;

Cheng, Joyce Y. ;

Chiesa-Fuxench, Zelma ;

Colegio, Oscar R. ;

Curiel-Lewandrowski, Clara ;

Del Guzzo, Christina A. ;

Disse, Max ;

Dowd, Margaret ;

Eilers, Robert, Jr. ;

Ortiz, Arisa Elena ;

Morris, Caroline ;

Golden, Spring K. ;

Graves, Michael S. ;

Griffin, John R. ;

Hopkins, Samuel ;

Huang, Conway C. ;

Bae, Gordon Hyeonjin ;

Jambusaria, Anokhi ;

Jennings, Thomas A. ;

Jiang, Shang I. Brian ;

Karia, Pritesh S. ;

Khetarpal, Shilpi ;

Kim, Changhyun ;

Klintmalm, Goran ;

Konicke, Kathryn ;

Koyfman, Shlomo A. ;

Lam, Charlene ;

Lee, Peter ;

Leitenberger, Justin J. ;

Loh, Tiffany ;

Lowenstein, Stefan ;

Madankumar, Reshmi ;

Moreau, Jacqueline F. ;

Nijhawan, Rajiv I. ;

Ochoa, Shari ;

Olasz, Edit B. ;

Otchere, Elaine ;

Otley, Clark ;

Oulton, Jeremy ;

Patel, Parth H. ;

Patel, Vishal Anil .

JAMA DERMATOLOGY, 2017, 153 (03) :296-303

[15]

Griffin Liezel L, 2018, JAAD Case Rep, V4, P229, DOI 10.1016/j.jdcr.2017.09.028

[16] 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-+

[17] Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis [J].

Grulich, Andrew E. ;

van Leeuwen, Marina T. ;

Falster, Michael ;

Vajdic, Claire M. .

LANCET, 2007, 370 (9581) :59-67

[18] Stevens-Johnson Syndrome Induced by Pembrolizumab in a Lung Cancer Patient [J].

Haratake, Naoki ;

Tagawa, Tetsuzo ;

Hirai, Fumihiko ;

Toyokawa, Gouji ;

Miyazaki, Reiko ;

Maehara, Yoshihiko .

JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (11) :1798-1799

[19] Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy [J].

Hwang, Andrew ;

Iskandar, Andrew ;

Dasanu, Constantin A. .

JOURNAL OF ONCOLOGY PHARMACY PRACTICE, 2019, 25 (06) :1520-1522

[20] Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma [J].

Jansen, Y. J. L. ;

Rozeman, E. A. ;

Mason, R. ;

Goldinger, S. M. ;

Foppen, M. H. Geukes ;

Hoejberg, L. ;

Schmidt, H. ;

van Thienen, J., V ;

Haanen, J. B. A. G. ;

Tiainen, L. ;

Svane, I. M. ;

Makela, S. ;

Seremet, T. ;

Arance, A. ;

Dummer, R. ;

Bastholt, L. ;

Nyakas, M. ;

Straume, O. ;

Menzies, A. M. ;

Long, G., V ;

Atkinson, V ;

Blank, C. U. ;

Neyns, B. .

ANNALS OF ONCOLOGY, 2019, 30 (07) :1154-1161

← 1 2 3 4 5 6 →