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Abemaciclib plus abiraterone did not improve outcomes in mCRPC, authors report

In this randomised, placebo-controlled study, adding a CDK4/6 inhibitor did not improve outcomes in mCRPC; the authors say further research is needed on possible subgroup benefit.

  • Matthew Smith, MD PhD; Josep Piulats, MD PhD; Tilman Todenhöfer, MD PhD; Jae-Lyun Lee, MD PhD; José Arranz Arija, MD; Laura Mazilu, MD PhD; et al.

  • November 1, 2025

  • The Lancet Oncology
  • The Lancet Oncology, Volume 26, Issue 11, Pages 1489–1500
  • 10.1016/S1470-2045(25)00475-9

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Evidence before this study

We searched PubMed and MEDLINE for peer-reviewed, original studies published in English from database inception to Nov 19, 2024, using the search terms “Cyclin-Dependent Kinase 4/6”, “CDK4/6 inhibitors”, and “Prostate Cancer.” We also reviewed key urological oncology journals and congress abstracts. Our search identified five studies. Two studies involved palbociclib: a phase 2 study of palbociclib added to combined androgen blockade in patients with retinoblastoma-associated protein-positive metastatic castration-sensitive prostate cancer (mCSPC; ) and a phase 2 biomarker umbrella trial for patients with metastatic castration-resistant prostate cancer (mCRPC; ). Three involved ribociclib: a phase 1b/2 of ribociclib added to enzalutamide for mCRPC (), a phase 1b/2 of ribociclib added to docetaxel for mCRPC (), and a study protocol for a phase 2 pharmacodynamic study of ribociclib in high-risk, localised prostate cancer (ACTRN12618000354280). Only one study (palbociclib plus combined androgen blockade in retinoblastoma-associated protein-positive mCSPC) was completed and reported final results in 2021, while CYCLONE 2 was ongoing.

Added value of this study

There is a pressing need for new treatments and combinations to improve the outcomes of patients with advanced prostate cancer. To our knowledge, CYCLONE 2 is the first randomised, placebo-controlled study to report the safety and efficacy of adding a CDK4 or CDK6 inhibitor to androgen receptor pathway inhibitor therapy in patients with prostate cancer.

Implications of all the available evidence

The combination of CDK4 and CDK6 inhibitors with endocrine therapy has become the standard of care for patients with hormonally driven breast cancer. Although evidence suggests that CDK4 and CDK6 signalling is a promising target for advanced prostate cancer treatment, potentially enhancing the efficacy of androgen receptor pathway inhibition, our findings suggest that the addition of abemaciclib to standard abiraterone therapy does not improve outcomes in patients with mCRPC. Further research is required to establish whether specific subgroups of patients, such as those with poor prognostic features, might benefit from this combination. The safety profile of combining abemaciclib with abiraterone acetate was consistent with the previously reported safety profiles of the individual drugs.

Source: The Lancet Oncology

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