A Signal-Finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer : Results from CYCLONE 1
Agarwal, Neeraj (University of Utah)
Castellano, Daniel (Hospital 12 de Octubre (Madrid))
Alonso-Gordoa, Teresa (Hospital Universitario Ramón y Cajal (Madrid))
Arranz Arija, José Ángel (Hospital General Universitario Gregorio Marañón)
Colomba, Emeline (Gustave Roussy Cancerology Institute)
Gravis, Gwenaelle (Institut Paoli-Calmettes)
Mourey, Loïc (IUCT-Oncopole Claudius Regaud)
Oudard, Stephane (University Paris Cité)
Fléchon, Aude (Cancérologie Médicale. Centre Léon-Bérard)
González, Macarena (Vall d'Hebron Institut d'Oncologia)
Maroto Rey, Pablo (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Schweizer, Michael T. (University of Washington)
Gallardo, Enrique (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Johnston, Erica (Eli Lilly and Company)
Balar, Arjun (Eli Lilly and Company)
Haddad, Nadine (Eli Lilly and Company)
Appiah, Adams K. (Eli Lilly and Company)
Nacerddine, Karim (Eli Lilly and Company)
Piulats, Josep M (Institut Catala d'Oncologia)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Purpose: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer. This study was designed to detect signals of clinical activity for abemaciclib in treatment-refractory metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods: Eligible patients had progressive mCRPC, measurable disease, and previously received ≥1 novel hormonal agent(s) and 2 lines of taxane chemotherapy. Abemaciclib 200 mg twice daily was administered on a continuous dosing schedule. Primary endpoint was objective response rate (ORR) without concurrent bone progression. This study was designed to detect a minimum ORR of 12. 5%. Results: At trial entry, 40 (90. 9%) of 44 patients had objective radiographic disease progression, 4 (9. 1%) had prostate-specific antigen (PSA)-only progression, and 20 (46. 5%) had visceral metastases (of these, 60% had liver metastases). Efficacy analyses are as follows: ORR without concurrent bone progression: 6. 8%; disease control rate: 45. 5%; median time to PSA progression: 6. 5 months [95% confidence interval (CI), 3. 2-NA]; median radiographic PFS; 2. 7 months (95% CI, 1. 9-3. 7); and median OS, 8. 4 months (95% CI, 5. 6-12. 7). Most frequent grade ≥3 treatment-emergent adverse events (AE) were neutropenia (25. 0%), anemia, and fatigue (11. 4% each). No grade 4 or 5 AEs were related to abemaciclib. Conclusions: Abemaciclib monotherapy was well tolerated and showed clinical activity in this heavily pretreated population, nearly half with visceral metastases. This study is considered preliminary proof-of-concept and designates CDK4/6 as a valid therapeutic target in prostate cancer.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aged ; Aged, 80 and over ; Aminopyridines ; Benzimidazoles ; Cyclin-Dependent Kinase 4 ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prostatic Neoplasms, Castration-Resistant ; Protein Kinase Inhibitors ; Treatment Outcome
Publicat a:	Clinical Cancer Research, Vol. 30 Núm. 11 (january 2024) , p. 2377-2383, ISSN 1557-3265

DOI: 10.1158/1078-0432.CCR-23-3436
PMID: 38512117

7 p, 1.2 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d’Investigació i Innovació Parc Taulí (I3PT)
Articles > Articles de recerca
Articles > Articles publicats