Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas.
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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, Groupe de Cancérologie Cutanée30
Аннотация
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.