Charlotte Domblides1, Karen Leroy2, Isabelle Monnet3, Julien Mazières4, Fabrice Barlesi5, Valérie Gounant6, Simon Baldacci7, Bertrand Mennecier8, Anne-Claire Toffart9, Clarisse Audigier-Valette10, Ludovic Doucet11, Etienne Giroux-Leprieur12, Florian Guisier13, Charles Ricordel14, Olivier Molinier15, Maurice Perol16, Eric Pichon17, Gilles Robinet18, Dorine Templement-Grangerat19, Anne-Marie Ruppert20, Nathalie Rabbe21, Martine Antoine22, Marie Wislez23. 1. Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital-CHU Bordeaux, Bordeaux, France; ImmunoConcEpt, CNRS UMR 5164, University of Bordeaux, Bordeaux, France. 2. Genetic and Molecular Biology Department, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France. 3. Department of Pneumology, CHI de Créteil, Créteil, France. 4. Department of Pneumology, Hôpital Larrey, Université Paul Sabatier, Toulouse, France. 5. Multidisciplinary Oncology & Therapeutic Innovations Department, Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France. 6. Thoracic Oncology Department, Hôpital Bichat, Paris, France. 7. Thoracic Oncology Department, Lille University Hospital, Lille, France. 8. Department of Pneumology, Hôpital Civil, Strasbourg, France. 9. Department of Pneumology, CHU Grenoble Alpes, France. 10. Department of Pneumology, CH Sainte Musse, Toulon, France. 11. Department of Medical Oncology, Hôpital Saint-Louis, Paris, France. 12. Department of Pneumology, Hôpital Ambroise Paré, Paris, France. 13. Department of Pneumology, Hôpital Charles Nicolle, Rouen, France. 14. Department of Pneumology, CHU Rennes, France. 15. Department of Pneumology, Hôpital du Mans, France. 16. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 17. Department of Pneumology, CHRU Bretonneau, Tours, France. 18. Department of Pneumology, CHRU Morvan, Brest, France. 19. Department of Pneumology, CH Annecy-Genevois, Saint-Julien-en-Genevois, France. 20. Sorbonne Université, GRC n°04, Theranoscan, Paris, France; Department of Pneumology, AP-HP, Groupe Hospitalier HUEP, Hôpital Tenon, Paris, France. 21. Department of Thoracic Oncology, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France; Centre de Recherche des Cordeliers, Université Paris Descartes, Complement, Inflammation and Cancer, Paris, France. 22. Pathology Department, AP-HP, Groupe Hospitalier HUEP, Hôpital Tenon, Paris, France. 23. Department of Thoracic Oncology, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France; Centre de Recherche des Cordeliers, Université Paris Descartes, Complement, Inflammation and Cancer, Paris, France. Electronic address: marie.wislez@aphp.fr.
Abstract
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.
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.
Authors: Roberto Ferrara; Diego Signorelli; Claudia Proto; Arsela Prelaj; Marina Chiara Garassino; Giuseppe Lo Russo Journal: Transl Lung Cancer Res Date: 2021-06