Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas
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Marie Beylot-Barry
- Fonction : Auteur
- PersonId : 762790
- ORCID : 0000-0001-6150-1229
- IdRef : 05956427X
Jean-Jacques Grob
- Fonction : Auteur
- PersonId : 762680
- ORCID : 0000-0002-1014-4062
Nicolas Meyer
- Fonction : Auteur
- PersonId : 800819
- ORCID : 0000-0003-4519-8666
- IdRef : 16890084X
Monica Dinulescu
- Fonction : Auteur
- PersonId : 781815
- ORCID : 0000-0002-3950-4340
Laurent Machet
- Fonction : Auteur
- PersonId : 908327
- ORCID : 0000-0001-5985-878X
- IdRef : 059215917
Olivier Dereure
- Fonction : Auteur
- PersonId : 759260
- ORCID : 0000-0001-8736-1922
Henri Montaudié
- Fonction : Auteur
- PersonId : 798589
- ORCID : 0000-0002-0528-4829
Yannick Le Corre
- Fonction : Auteur
- PersonId : 777129
- ORCID : 0000-0003-3089-3068
Sophie Dalac
- Fonction : Auteur
- PersonId : 762781
- ORCID : 0000-0002-9101-3119
Résumé
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 (ORR W15 ). 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 W15 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 ORR W15 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 W15 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.