Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas
| Autor: | Coralie Bloch-Queyrat, Florent Grange, Lydia Deschamps, Sandrine Mansard, Nicole Basset-Seguin, Annick Tibi, Vincent Levy, Sarah Guégan, D. Legoupil, Jean-Philippe Arnault, Henri Montaudié, Marouane Boubaya, Olivier Dereure, Yannick Le Corre, A. Stefan, François Aubin, Céline Alloux, Jean-Jacques Grob, Peter Petrow, Soufian Cherbal, Groupe de cancérologie cutanée, Philippe Saiag, Nicolas Meyer, Isabelle Lopez, Marie Beylot-Barry, Eve Maubec, Marie-Thérèse Leccia, Brigitte Dréno, Ouidad Zehou, Laurent Machet, Julie De Quatrebarbes, Sophie Dalac, Monica Dinulescu, E. Wierzbicka-Hainaut, Isabelle Scheer-Senyarich |
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| Přispěvatelé: | Herrada, Anthony, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Polyclinique Saint Côme, Institut Curie [Paris], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Grenoble, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Hôpital Cochin [AP-HP], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research Skin Neoplasms Time Factors MESH: Immune Checkpoint Inhibitors Cell Phases of clinical research Pembrolizumab B7-H1 Antigen Antineoplastic Agents Immunological 0302 clinical medicine MESH: Aged 80 and over MESH: Progression-Free Survival MESH: B7-H1 Antigen Medicine Immune Checkpoint Inhibitors Aged 80 and over MESH: Aged MESH: Middle Aged MESH: Carcinoma Squamous Cell Middle Aged Progression-Free Survival 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Monoclonal Carcinoma Squamous Cell Disease Progression Female MESH: Disease Progression France Adult medicine.medical_specialty [SDV.CAN]Life Sciences [q-bio]/Cancer Antibodies Monoclonal Humanized 03 medical and health sciences Pharmacotherapy [SDV.CAN] Life Sciences [q-bio]/Cancer Internal medicine Carcinoma Humans Progression-free survival Aged MESH: Humans business.industry MESH: Skin Neoplasms MESH: Time Factors MESH: Quality of Life MESH: Adult medicine.disease MESH: Antineoplastic Agents Immunological MESH: Male Clinical trial MESH: France 030104 developmental biology MESH: Antibodies Monoclonal Humanized Quality of Life business MESH: Female |
| Zdroj: | Journal of Clinical Oncology Journal of Clinical Oncology, 2020, 38 (26), pp.3051-3061. ⟨10.1200/JCO.19.03357⟩ Journal of Clinical Oncology, American Society of Clinical Oncology, 2020, 38 (26), pp.3051-3061. ⟨10.1200/JCO.19.03357⟩ |
| ISSN: | 0732-183X 1527-7755 |
| DOI: | 10.1200/JCO.19.03357 |
| Popis: | PURPOSE To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS Patients, predominantly men, with their CSSCs’ immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort’s objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy–General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1– patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS Median age of all patients was 79 years. The primary cohort’s ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1– patients (17%; P = .02). Responders’ W15 total FACT-G score had improved ( P = .025) compared with nonresponders. CONCLUSION First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy. |
| Databáze: | OpenAIRE |
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