Phase I Study of Androgen Deprivation Therapy in Combination with Anti-PD-1 in Melanoma Patients Pretreated with Anti-PD-1.
Fiche du document
1 mars 2023
- doi: 10.1158/1078-0432.CCR-22-2812
- issn: 1078-0432
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-22-2812
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/36516188
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1557-3265
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_04775354DA151
info:eu-repo/semantics/embargoedAccess , Restricted: cannot be viewed until 2024-03-01 , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Melanocytic tumor Malignant melanomaCiter ce document
C. Robert et al., « Phase I Study of Androgen Deprivation Therapy in Combination with Anti-PD-1 in Melanoma Patients Pretreated with Anti-PD-1. », Serveur académique Lausannois, ID : 10.1158/1078-0432.CCR-22-2812
Métriques
Partage / Export
Résumé
Androgen deprivation regenerates the thymus in adults, expanding of T-cell receptor V β repertoire in blood and lymphoid organs and tumor-infiltrating lymphocytes in human prostate tumors. In melanoma murine models, androgen receptor promotes metastases and androgen blockade potentiates antitumor vaccine efficacy. This phase I study evaluated the safety, efficacy, and pharmocodynamics of androgen deprivation with the gonadotropin releasing hormone (GnRH) agonist triptorelin combined with nivolumab in male patients with melanoma resistant to anti-PD-1. Adult male patients with advanced melanoma who progressed under anti-PD-1 containing regimens received triptorelin 3.75 mg every 4 weeks, nivolumab 3 mg/kg every 2 weeks, and bicalutamide 50 mg once daily during the first 28 days. Tumor response was first assessed after 3 months; adverse events (AE) were monitored throughout the study. T-cell receptor excision circles (TREC), a biomarker of thymus activity, were explored throughout the study. Of 14 patients, 4 were locally advanced and 10 had distant metastases. There were no grade 4 or 5 AEs. Five grade three AEs were reported in 4 patients. According to RECIST v1.1, best overall response was partial response (PR) in one patient with a pancreas metastasis, stable disease (SD) in 5 patients, and progressive disease in 8 patients. According to iRECIST, a second PR occurred after an initial pseudoprogression, TRECs increased in 2 patients, one with PR who also had an increase in TILs, and the second with SD. This combination was well tolerated. Disease control was obtained in 42.8% (RECIST) and 50% (iRECIST). The evidence for thymus rejuvenation was limited.