Agarwal, NeerajCastellano, DanielAlonso Gordoa, TeresaArranz Arija, José ÁngelColomba, EmelineGravis, GwenaelleMourey, LoicOudard, StephaneFléchon, AudeGonzález, MacarenaRey, Pablo M.Schweizer, Michael T.Gallardo, EnriqueJohnston, EricaBalar, ArjunHaddad, NadineAppiah, Adams K.Nacerddine, KarimPiulats, Josep M.2024-09-032024-09-032024-03-211557-3265https://hdl.handle.net/2445/214957Purpose: 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.7 p.application/pdfengcc by-nc-nd (c) Agarwal, Neeraj et al, 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/Càncer de pròstataAndrògensProstate cancerAndrogensinfo:eu-repo/semantics/article2024-07-01info:eu-repo/semantics/openAccess38512117