ASCO 2020: CYCLONE 2: A Phase II, Randomized, Placebo-Controlled Study of Abiraterone Acetate plus Prednisone with or Without Abemaciclib in Patients with Metastatic Castration-Resistant Prostate Cancer

( The cyclin-dependent kinase proteins CDK4 and CDK6 modulate cell cycle progression by phosphorylating and thus inactivating the RB protein. Inhibition of these proteins in breast cancer with multiple agents including abemaciclib is approved both in combination with endocrine therapy or as monotherapy in advanced hormone-receptor-positive disease. As discussed in Abstract 5573, prior phase 2 studies of CDK4/6 inhibition with older androgen receptor antagonists showed no difference in responses, but this may be different within combination with new-antiandrogen therapies. 

In this study, Matthew Smith, MD, PhD, and colleagues layout the design of the randomized, placebo-controlled phase 2 study of standard of care abiraterone acetate +/- the CDK4/6 inhibitor abemaciclib in patients with metastatic castration-resistant prostate cancer. The trial schema is shown below. Co-primary objectives will be radiographic progression-free survival and time to PSA progression. Key secondary objectives are safety, objective response rate, time to symptomatic progression, pharmacokinetics, and overall survival. To be included in the study, patients must have mCRPC, pre-treatment biopsy, and adequate organ function to tolerate therapy. Prior chemotherapy for mCRPC is allowed, but prior treatment with CDK4/6 inhibitor, Provenge, radiopharmaceuticals or AR antagonists is not allowed. 


The study is designed with a safety lead-in (part 1) to determine the recommended phase 2 dose of abemaciclib in combination with abiraterone. Once the RP2D dose is determined, 150 patients will be enrolled and randomized for therapy. Assuming a hazard ratio of 0.64, the study has 80% power to test the superiority of abemaciclib combination therapy at an alpha of 0.1. 

As of the time of this poster, part 1 has been completed, and part 2 is enrolling at 72 sites in 9 countries (Australia, Denmark, Germany, Netherlands, Romania, South Korea, Spain, UK, USA). 

Presented by: Matthew R. Smith, MD, PhD, Director of the Genitourinary Malignancies Program and Professor of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 American Society of Clinical Oncology virtual annual meeting (#ASCO20), May 29th-May 31st, 2020

Related Content: 
Clinical Trial Information:  NCT03706365 - A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer (CYCLONE 2)