A Signal-Finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration–Resistant Prostate Cancer: Results from CYCLONE 1

Abstract

Abemaciclib; Pretreated; Metastatic prostate cancer

Abemaciclib; Pretractats; Càncer de pròstata metastàtic

Abemaciclib; Pretratados; Cáncer de próstata metastásico

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.

This work was funded by Eli Lilly and Company. Medical writing was provided by Trish Huynh, employee of Eli Lilly and Company. Eli Lilly and Company contracted with Syneos Health for editorial support from Antonia Baldo. We thank the participants and their families or caregivers for participating in this trial. CYCLONE 1 would not have been possible without the investigators and their support staff who participated in this work.