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). 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.
Subject(s)
Aminopyridines , Benzimidazoles , Prostatic Neoplasms, Castration-Resistant , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Aminopyridines/adverse effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/administration & dosage , Treatment OutcomeABSTRACT
OBJETIVO: El objetivo de este estudio es describir la experiencia inicial en nuestro centro de las primeras 94 Biopsias de Próstata dirigidas (BD) con fusión de imagen ecografía/Resonancia magnética (US/RMmp) y comparar la tasa de detección de CaP con las biopsias sistemáticas. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y comparativo de los primeros 94 pacientes sometidos a BD por fusión de imagen US/RMmp en nuestro centro desde febrero de 2017 hasta marzo de 2018. Todos los pacientes fueron sometidos a un protocolo de 6-12 cilindros de biopsias sistemáticas (BS) (menos 9) y de 2-6 cilindros dirigidos a las lesiones diana visualizadas en la RMmp. Se utilizó el equipo Hitachi/HiVision Preirus con software RVS (Real-time virtual sonography) y un transductor biplanar para la fusión de imagen. Se definió como CaP clínicamente significativo un GS ≥ 3 + 4 en, al menos, 1 de los cilindros realizados. RESULTADOS: La proporción de detección de CaP fue mayor en las BD que en las BS (p = 0,035) y el número de cilindros realizados para su diagnóstico fue menor en las BD comparado con las BS (p < 0,001). Se observó una clara tendencia a una mayor identificación de CaP clínicamente significativo (CaPcs) en las BD comparado con las BS (p = 0,063). CONCLUSIONES: Comparado con las BS, las BD por fusión de imagen US/RMmp presentaron una mayor tasa de detección de CaP y una tendencia a una mayor identificación de CaPcS con una necesidad menor de cilindros realizados
OBJECTIVE: To describe the initial experience in our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB). PATIENTS AND METHODS: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted cores on the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusión imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4. RESULTS: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p = 0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p < 0.001). A trend towards an improved detection of csPCa in TB compared to SB was observed (p = 0.063). CONCLUSIONS: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with les cores taken for diagnosis and a tendency to better identification of csCaP compared to SB