Eve Maubec1,2, Marouane Boubaya1, Peter Petrow3,4, Marie Beylot-Barry5, Nicole Basset-Seguin6, Lydia Deschamps7, Jean-Jacques Grob8, Brigitte Dréno9, Isabelle Scheer-Senyarich1, Coralie Bloch-Queyrat1, Marie-Thérèse Leccia10, Andreea Stefan11, Philippe Saiag12, Florent Grange13, Nicolas Meyer14, Julie de Quatrebarbes15, Monica Dinulescu16, Delphine Legoupil17, Laurent Machet18, Olivier Dereure19, Ouidad Zehou20, Henri Montaudié21, Ewa Wierzbicka-Hainaut22, Yannick Le Corre23, Sandrine Mansard24, Sarah Guégan25, Jean-Philippe Arnault26, Sophie Dalac27, François Aubin28, Céline Alloux29, Isabelle Lopez3, Soufian Cherbal1, Annick Tibi29, Vincent Lévy1,2. 1. Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France. 2. Université Paris 13, Bobigny, France. 3. Association de Cabinet de Radiologie et d'Imagérie Médicale, Service de Radiologie, Polyclinique Saint-Côme, Compiègne, France. 4. Institut Curie, Service de Radiodiagnostic, Paris, France. 5. Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. 6. Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France. 7. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France. 8. Hôpital de la Timone, Marseille, France. 9. Service Oncodermatologie, Centre Hospitalier Universitaire Nantes, Centre d'Investigation Clinique 1413, Centre de Recherche en Cancérologie et Immunologie Nantes Angers, Université de Nantes, Nantes, France. 10. Centre Hospitalier Universitaire de Grenoble, Genoble, France. 11. Centre Hospitalier Universitaire de Caen, Caen, France. 12. Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise-Paré, Boulogne, France. 13. Centre Hospitalier Universitaire Reims, Hôpital Robert-Debré, Reims, France. 14. Institut Universitaire du Cancer and Centre Hospitalier Universitaire de Toulouse, Toulouse, France. 15. Centre Hospitalier Genevois, Pringy, France. 16. Centre Eugène-Marquis, Rennes, France. 17. Centre Hospitalier Régional Universitaire de Brest, Brest, France. 18. Centre Hospitalier Régional Universitaire de Tours, Chambray-les-Tours, France. 19. Université de Montpellier, Montpellier, France. 20. Assistance Publique-Hôpitaux de Paris, Hôpital Henri-Mondor, Créteil, France. 21. Hôpital Archet 2, Centre Hospitalier Universitaire de Nice, Nice, France. 22. Centre Hospitalier Universitaire La Milétrie, Poitiers, France. 23. Centre Hospitalier Universitaire d'Angers, Angers, France. 24. Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, Clermont-Ferrand, France. 25. Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France. 26. Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France. 27. Centre Hospitalier Universitaire de Dijon, Dijon, France. 28. Centre Hospitalier Régional Universitaire Besançon, France. 29. Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, Paris, France.
Abstract
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.
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.
Authors: Sofian Benkhaled; Dirk Van Gestel; Carolina Gomes da Silveira Cauduro; Samuel Palumbo; Veronique Del Marmol; Antoine Desmet Journal: Front Med (Lausanne) Date: 2022-06-27
Authors: Neil K Mehta; Andraia R Li; Shaun A Nguyen; John M Kaczmar; David M Neskey; Terry A Day Journal: Target Oncol Date: 2021-10-22 Impact factor: 4.864
Authors: Danny Rischin; Nikhil I Khushalani; Chrysalyne D Schmults; Alexander Guminski; Anne Lynn S Chang; Karl D Lewis; Annette M Lim; Leonel Hernandez-Aya; Brett G M Hughes; Dirk Schadendorf; Axel Hauschild; Alesha A Thai; Elizabeth Stankevich; Jocelyn Booth; Suk-Young Yoo; Siyu Li; Zhen Chen; Emmanuel Okoye; Chieh-I Chen; Vera Mastey; Medha Sasane; Israel Lowy; Matthew G Fury; Michael R Migden Journal: J Immunother Cancer Date: 2021-08 Impact factor: 13.751