Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas

• Published in: Journal of clinical oncology Vol. 38; no. 26; pp. 3051 - 3061
• Main Authors: Maubec, Eve, Boubaya, Marouane, Petrow, Peter, Beylot-Barry, Marie, Basset-Seguin, Nicole, Deschamps, Lydia, Grob, Jean-Jacques, Dréno, Brigitte, Scheer-Senyarich, Isabelle, Bloch-Queyrat, Coralie, Leccia, Marie-Thérèse, Stefan, Andreea, Saiag, Philippe, Grange, Florent, Meyer, Nicolas, de Quatrebarbes, Julie, Dinulescu, Monica, Legoupil, Delphine, Machet, Laurent, Dereure, Olivier, Zehou, Ouidad, Montaudié, Henri, Wierzbicka-Hainaut, Ewa, Le Corre, Yannick, Mansard, Sandrine, Guégan, Sarah, Arnault, Jean-Philippe, Dalac, Sophie, Aubin, François, Alloux, Céline, Lopez, Isabelle, Cherbal, Soufian, Tibi, Annick, Lévy, Vincent
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.09.2020
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Cancer; Carcinoma, Squamous Cell; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Disease Progression; Female; France; Humans; Immune Checkpoint Inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Life Sciences; Male; Middle Aged; Progression-Free Survival; Quality of Life; Skin Neoplasms; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Time Factors; France
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.19.03357

To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). 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 (ORR ). 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 ORR difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival. Median age of all patients was 79 years. The primary cohort's ORR 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. ORR for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; = .02). Responders' W15 total FACT-G score had improved ( = .025) compared with nonresponders. 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.