Prostate cancer: new indication recommended in EU for patients with metastatic disease

Facing a diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) is an experience that can radically change the life of a man and his family. For this reason, every step forward in research represents a concrete possibility. The Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended darolutamide – an oral androgen receptor inhibitor (ARi) – in combination with androgen deprivation therapy (ADT), for marketing authorization in the European Union for the treatment of metastatic hormone-sensitive prostate cancer.

10% of patients diagnosed in metastatic stage

Prostate cancer is the second most common cancer and the fifth leading cause of cancer death among men globally. In 2022, there will be an estimated 1.5 million new diagnoses and approximately 397,000 deaths worldwide. In Europe, in the same year, there were approximately 474,000 new cases and 115,000 deaths. By 2040, diagnoses are expected to reach 2.9 million. At the onset, most prostate cancers are localized, potentially curable with surgery or radiotherapy. However, up to 10% of men are diagnosed directly in the hormone-sensitive metastatic stage. For these patients, ADT – combined with chemotherapy or ARi – is the mainstay of treatment. However, many progress to a castration-resistant form, limiting options.

The Aranote Study

The European Medicines Agency’s recommendation comes in light of data from the pivotal Phase III Aranote study. This randomized, double-blind, placebo-controlled study involved 669 patients with hormone-sensitive metastatic prostate cancer, assigned to receive 600 mg of darolutamide twice daily or placebo, both in addition to ADT. The primary endpoint was radiological progression-free survival (rPFS), while secondary endpoints included overall survival, castration resistance, PSA progression, and tolerability. Data presented at Esmo 2024 and published in the Journal of Clinical Oncology showed a significant reduction in the risk of radiological progression or death of 46% in patients treated with darolutamide plus androgen deprivation therapy (ADT) compared to those treated with placebo plus ADT. Efficacy was also demonstrated in the subgroups with high-volume and low-volume disease. The treatment was found to be well tolerated, with an incidence of adverse events – including serious ones – comparable to the placebo.

Benefits for patients

Currently, darolutamide is authorized in over 85 countries, both in combination with ADT and docetaxel for hormone-sensitive metastatic prostate cancer, and with ADT alone for the treatment of non-metastatic castration-resistant prostate cancer in patients at high risk of developing metastases. “In 2024, in Italy, approximately 40,200 new diagnoses of prostate cancer were estimated, the most frequent in men in our country,” emphasizes Orazio Caffo, director of Oncology at the Santa Chiara Hospital in Trento. “The impact of metastatic prostate cancer on the daily lives of those who suffer from it can be very significant. The Aranote study has shown that darolutamide, a new-generation oral androgen receptor inhibitor, combined with androgen deprivation therapy alone, significantly reduces the risk of radiological progression or death. This treatment has also shown significant benefits in terms of quality of life. This enriches the therapeutic arsenal of clinicians, making possible an even more personalized approach to combat a particularly insidious form of prostate cancer”.

Darolutamide: characteristics and future prospects

Darolutamide is an oral androgen receptor inhibitor with a unique chemical structure that binds to the androgen receptor with high affinity and blocks its function, thereby inhibiting tumor growth. Preclinical studies and neuroimaging data suggest low blood-brain barrier penetration, which may contribute to a good tolerability profile. The final decision by the European Commission on marketing authorization is expected in the coming months. In the meantime, the US Food and Drug Administration (FDA) has already approved darolutamide, in June 2025, in combination with ADT – with or without chemotherapy – as the first androgen receptor inhibitor approved in the US for the treatment of mHSPC.