Phase 3 Trial Shows Limited Benefit of Abemaciclib With Abiraterone in Metastatic Prostate Cancer

A team of researchers, led by Matthew Raymond Smith, MD, PhD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, in Boston, Massachusetts, investigated whether the addition of abemaciclib (ABEMA), a potent CDK4/6 inhibitor, to abiraterone (ABI) improves treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). The research was presented at the 2024 American Society of Clinical Oncology Annual Meeting.

CYCLONE 2, a phase 3 study, aimed to evaluate the efficacy and safety of ABEMA plus ABI compared with ABI alone in patients with first-line mCRPC. The rationale behind this combination stemmed from preclinical evidence suggesting the role of CDK4/6 in sustaining androgen receptor signaling and promoting resistance to hormonal therapy in prostate cancer.

Between November 2018 and July 2022, 393 patients were enrolled and randomized. The primary end point of investigator-assessed radiographic progression-free survival (rPFS) did not show a significant improvement with the addition of ABEMA to ABI (hazard ratio [HR], 0.829; P=.2123). Median rPFS was 21.96 months for the ABEMA plus ABI group and 20.28 months for the ABI alone group. This finding was consistent with blinded independent central review.

Overall survival, a secondary end point, was not inferentially tested (HR, 0.927; 95% CI, 0.669-1.285; 38.9% maturity). Secondary end points, including time to prostate-specific antigen progression, time to symptomatic progression, and time to worst pain progression, did not demonstrate meaningful improvements with the combination therapy.

The safety profile revealed that the most common grade ≥3 adverse events (AEs) in the ABEMA plus ABI group were anemia, neutropenia, and increased alanine transaminase levels. However, discontinuations of all study treatments due to AEs were higher in the ABEMA plus ABI group compared with the ABI alone group.

Researchers concluded the addition of ABEMA to ABI did not significantly enhance rPFS or secondary end points in patients with mCRPC. While the combination therapy was generally well tolerated, it did not demonstrate a clear clinical benefit over ABI alone. Further investigations may be warranted to explore alternative treatment strategies in this patient population.

This study underscores the complexity of treating advanced prostate cancer and the importance of continued research efforts to identify more effective therapeutic approaches.