RT Journal Article
SR Electronic
T1 Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002996
DO 10.1136/jitc-2021-002996
VO 9
IS 11
A1 Sara Lonardi
A1 Alessandra Anna Prete
A1 Federica Morano
A1 Marco Messina
A1 Vincenzo Formica
A1 Domenico Cristiano Corsi
A1 Corrado Orciuolo
A1 Giovanni Luca Frassineti
A1 Maria Giulia Zampino
A1 Mariaelena Casagrande
A1 Gianluca Masi
A1 Monica Ronzoni
A1 Mario Scartozzi
A1 Angela Buonadonna
A1 Stefania Mosconi
A1 Margherita Ratti
A1 Andrea Sartore-Bianchi
A1 Emiliano Tamburini
A1 Michele Prisciandaro
A1 Francesca Bergamo
A1 Massimiliano Spada
A1 Salvatore Corallo
A1 Valentina Vettore
A1 Fotios Loupakis
A1 Matteo Fassan
A1 Paola Del Bianco
A1 Vittorina Zagonel
A1 Filippo Pietrantonio
YR 2021
UL http://jitc.bmj.com/content/9/11/e002996.abstract
AB Background No standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC.Methods In this open-label, non-comparative, ‘pick the winner’, multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.Results Thirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4–74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5–26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms.Conclusions CARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC.Data are available on reasonable request.