Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma

被引：117

作者：

Domblides, Charlotte ^{[1
,2
]}

Leroy, Karen ^{[3
]}

Monnet, Isabelle ^{[4
]}

Mazieres, Julien ^{[5
]}

Barlesi, Fabrice ^{[6
]}

Gounant, Valerie ^{[7
]}

Baldacci, Simon ^{[8
]}

Mennecier, Bertrand ^{[9
]}

Toffart, Anne-Claire ^{[10
]}

Audigier-Valette, Clarisse ^{[11
]}

Doucet, Ludovic ^{[12
]}

Giroux-Leprieur, Etienne ^{[13
]}

Guisier, Florian ^{[14
]}

Ricordel, Charles ^{[15
]}

Molinier, Olivier ^{[16
]}

Perol, Maurice ^{[17
]}

Pichon, Eric ^{[18
]}

Robinet, Gilles ^{[19
]}

Templement-Grangerat, Dorine ^{[20
]}

Ruppert, Anne-Marie ^{[21
,22
]}

Rabbe, Nathalie ^{[23
,24
]}

Antoine, Martine ^{[25
]}

Wislez, Marie ^{[23
,24
]}

机构：

[1] CHU Bordeaux, Dept Med Oncol, Hop St Andre, Bordeaux Univ Hosp, Bordeaux, France

[2] Univ Bordeaux, ImmunoConcEpt, CNRS, UMR 5164, Bordeaux, France

[3] Grp Hosp HUPC, Genet & Mol Biol Dept, Hop Cochin, AP HP, Paris, France

[4] CHI Creteil, Dept Pneumol, Creteil, France

[5] Univ Paul Sabatier, Dept Pneumol, Hop Larrey, Toulouse, France

[6] Aix Marseille Univ, Multidisciplinary Oncol & Therapeut Innovat Dept, AP HM, CRCM,CNRS,INSERM, Marseille, France

[7] Hop Bichat Claude Bernard, Thorac Oncol Dept, Paris, France

[8] Lille Univ Hosp, Thorac Oncol Dept, Lille, France

[9] Hop Civil, Dept Pneumol, Strasbourg, France

[10] CHU Grenoble Alpes, Dept Pneumol, Grenoble, France

[11] CH St Musse, Dept Pneumol, Toulon, France

[12] Hop St Louis, Dept Med Oncol, Paris, France

[13] Hop Ambroise Pare, Dept Pneumol, Paris, France

[14] Hop Charles Nicolle, Dept Pneumol, Rouen, France

[15] CHU Rennes, Dept Pneumol, Rennes, France

[16] Hop Mans, Dept Pneumol, Le Mans, France

[17] Ctr Leon Berard, Dept Med Oncol, Lyon, France

[18] CHRU Bretonneau, Dept Pneumol, Tours, France

[19] CHRU Morvan, Dept Pneumol, Brest, France

[20] CH Annecy Genevois, Dept Pneumol, St Julien En Genevois, France

[21] Sorbonne Univ, Theranoscan, GRC 04, Paris, France

[22] Grp Hosp HUEP, Dept Pneumol, Hop Tenon, AP HP, Paris, France

[23] Grp Hosp HUPC, Dept Thorac Oncol, Hop Cochin, AP HP, Paris, France

[24] Univ Paris 05, Ctr Rech Cordeliers, Complement Inflammat & Canc, Paris, France

[25] Grp Hosp HUEP, Pathol Dept, Hop Tenon, AP HP, Paris, France

来源：

JOURNAL OF THORACIC ONCOLOGY | 2020年 / 15卷 / 05期

关键词：

Pulmonary sarcomatoid carcinoma; Immune check point inhibitor; PD-L1; Tumor mutational burden; SHOW HIGH-LEVELS; NIVOLUMAB; MUTATIONS; CANCER; PD-L1;

D O I：

10.1016/j.jtho.2020.01.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. Methods: All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. Results: Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). Conclusions: Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：860 / 866

页数：7

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