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A Signal-Finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer: Results from CYCLONE 1.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jun 03; Vol. 30 (11), pp. 2377-2383. - Publication Year :
- 2024
-
Abstract
- 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).<br />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%.<br />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.<br />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.<br /> (©2024 The Authors; Published by the American Association for Cancer Research.)
- Subjects :
- Aged
Aged, 80 and over
Humans
Male
Middle Aged
Cyclin-Dependent Kinase 4 antagonists & inhibitors
Neoplasm Metastasis
Protein Kinase Inhibitors therapeutic use
Protein Kinase Inhibitors adverse effects
Protein Kinase Inhibitors administration & dosage
Treatment Outcome
Aminopyridines administration & dosage
Aminopyridines therapeutic use
Aminopyridines adverse effects
Benzimidazoles administration & dosage
Benzimidazoles adverse effects
Benzimidazoles therapeutic use
Prostatic Neoplasms, Castration-Resistant drug therapy
Prostatic Neoplasms, Castration-Resistant pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 30
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 38512117
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-23-3436