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
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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