Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas
Eve Maubec
(1, 2)
,
Marouane Boubaya
(1)
,
Peter Petrow
(3, 4)
,
Marie Beylot-Barry
(5)
,
Nicole Basset-Seguin
(6)
,
Lydia Deschamps
(7)
,
Jean-Jacques Grob
(8)
,
Brigitte Dréno
(9, 10)
,
Isabelle Scheer-Senyarich
(1)
,
Coralie Bloch-Queyrat
(1)
,
Marie-Thérèse Leccia
(11)
,
Andreea Stefan
(12)
,
Philippe Saiag
(13)
,
Florent Grange
(14)
,
Nicolas Meyer
(15, 16)
,
Julie de Quatrebarbes
(17)
,
Monica Dinulescu
(18)
,
Delphine Legoupil
(19)
,
Laurent Machet
(20)
,
Olivier Dereure
(21, 22)
,
Ouidad Zehou
(23)
,
Henri Montaudié
(24)
,
Ewa Wierzbicka-Hainaut
(25)
,
Yannick Le Corre
(26)
,
Sandrine Mansard
(27)
,
Sarah Guégan
(28)
,
Jean-Philippe Arnault
(29)
,
Sophie Dalac
(30)
,
François Aubin
(31)
,
Céline Alloux
(32)
,
Isabelle Lopez
(3)
,
Soufian Cherbal
(1)
,
Annick Tibi
(32)
,
Vincent Lévy
(1, 2)
1
Hôpital Avicenne [AP-HP]
2 UP13 - Université Paris 13
3 Polyclinique Saint Côme
4 Institut Curie [Paris]
5 CHU Bordeaux
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
8 TIMONE - Hôpital de la Timone [CHU - APHM]
9 CIC Nantes - Centre d’Investigation Clinique de Nantes
10 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
11 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
12 CHU Caen
13 Hôpital Ambroise Paré [AP-HP]
14 Hôpital Robert Debré
15 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
18 CRLCC - CRLCC Eugène Marquis
19 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
20 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 Pathogénèse et contrôle des infections chroniques (PCCI)
23 Hôpital Henri Mondor
24 CHU Nice - Centre Hospitalier Universitaire de Nice
25 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
26 CHU Angers - Centre Hospitalier Universitaire d'Angers
27 CHU Clermont-Ferrand
28 Hôpital Cochin [AP-HP]
29 CHU Amiens-Picardie
30 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
31 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
32 AGEPS - Agence Générale des Equipements et Produits de Santé [Paris]
2 UP13 - Université Paris 13
3 Polyclinique Saint Côme
4 Institut Curie [Paris]
5 CHU Bordeaux
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
8 TIMONE - Hôpital de la Timone [CHU - APHM]
9 CIC Nantes - Centre d’Investigation Clinique de Nantes
10 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
11 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
12 CHU Caen
13 Hôpital Ambroise Paré [AP-HP]
14 Hôpital Robert Debré
15 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
18 CRLCC - CRLCC Eugène Marquis
19 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
20 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 Pathogénèse et contrôle des infections chroniques (PCCI)
23 Hôpital Henri Mondor
24 CHU Nice - Centre Hospitalier Universitaire de Nice
25 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
26 CHU Angers - Centre Hospitalier Universitaire d'Angers
27 CHU Clermont-Ferrand
28 Hôpital Cochin [AP-HP]
29 CHU Amiens-Picardie
30 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
31 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
32 AGEPS - Agence Générale des Equipements et Produits de Santé [Paris]
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
Marie-Thérèse Leccia
- Fonction : Auteur
- PersonId : 758597
- ORCID : 0000-0003-1222-0396
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.