A threesome works best and can improve survival in patients with metastatic hormone-sensitive prostate cancer. The winning ‘triangle’ is the one that combines the use of oral androgen receptor inhibitor darolutamide (ARi), plus androgen deprivation therapy (ADT) and docetaxel. The results of the Phase III ARASENS study, in fact, showed that used in combination significantly increase overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The findings were presented at the ASCO GU Cancers Symposium 2022 and simultaneously published in The New England Journal of Medicine.
even 2021
Prostate cancer: “nuclear therapy” improves the quality of life
The reduction of the risk of death
The ARASENS study in 1,306 patients with mHSPC disease was randomized in a 1: 1 ratio to receive darolutamide 600 mg twice daily or placebo, in addition to ADT and docetaxel. One of the most important data concerns the risk of death: darolutamide (jointly developed by Bayer and Orion Corporation), plus androgen deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel. At the data cutoff date for the primary analysis (25 October 2021), the median duration of treatment was longer for darolutamide plus ADT and docetaxel (41.0 months) than for ADT plus docetaxel (16.7 months). Darolutamide plus ADT and docetaxel also showed significant benefits in secondary endpoints and in pre-specified subgroups. Adverse event rates (AEs) did not increase with the addition of darolutamide.
Prostate cancer, effective drugs and a good quality of life
Very aggressive tumors
The arrival of these new data is a real breath of fresh air for patients: “Among the cases of advanced prostate cancer – he says Sergio Bracarda, director of the Oncology Department and of the Complex Structure of Medical and Translational Oncology of the Santa Maria di Terni Hospital and “incoming” President of SIUrO (Italian Society of Uro-Oncology) – those metastatic at diagnosis are to be considered, on average, as more aggressive and therefore to be treated more comprehensively as demonstrated in the recent past by the survival advantages obtained with chemotherapy with docetaxel in the early phase “. It is precisely in this perspective that doctors read the results of the ARASENS study: “These data – adds Bracarda – support a further advantage in survival (reduction of the risk of death by 32.5%) with the addition of darolutamide alone. Androgen deprivation combined with chemotherapy in hormone-sensitive metastatic disease, largely at diagnosis. Other secondary endpoints have also been achieved and all with good tolerability to the treatment “.
“Cocktail” of three drugs for metastatic prostate cancer
The commitment to make it available
Darolutamide has shown positive data in two phase III clinical trials, ARASENS in metastatic hormone-sensitive prostate cancer, and ARAMIS in non-metastatic castration-resistant prostate cancer (nmCRPC) for patients in these key stages of prostate cancer. Furthermore, darolutamide plus ADT and docetaxel also significantly delayed the time to pain progression compared to ADT plus docetaxel, the time to the first symptomatic skeletal event (and the time to start of subsequent systemic anticancer therapy. to make this new therapeutic option in hormone-sensitive metastatic prostate cancer available to patients and their doctors, and therefore are pursuing regulatory timelines as fast as possible.
The next studies
Darolutamide is approved in more than 60 markets around the world, including the United States, the European Union (EU), Japan and China, for the treatment of patients with nmCRPC at high risk of developing metastases. The molecule is being evaluated in further studies in the different stages of prostate cancer: among them another Phase III study in the mHSPC (ARANOTE) and a Phase III ANZUP-led study, an international cooperation group that evaluates darolutamide as a therapy. adjuvant in localized prostate cancer at high risk of recurrence.
Metastatic hormone-sensitive prostate cancer
Prostate cancer is the second largest cancer in the male population worldwide. It is estimated that 1.4 million men worldwide were diagnosed with prostate cancer in 2020 and about 375,000 men died of prostate cancer. Most men have localized cancer at the time of diagnosis, which means the cancer is confined to the prostate gland and can be treated with curative surgery or radiation therapy. In case of relapse, when the disease spreads or becomes metastatic, androgen deprivation therapy (ADT) is the mainstay of treatment. About 5% of men, at the first diagnosis, already have prostate cancer with distant metastases. Current treatment for men with metastatic hormone-sensitive prostate cancer (mHSPC) involves ADT, the combination of docetaxel and ADT chemotherapy, and the combination of ADT with other second-generation androgen receptor inhibitors. Despite these treatments, most patients with metastatic hormone-sensitive prostate cancer progress to castration-resistant cancer (mCRPC), a disease condition characterized by limited survival.