Prostate cancer, 'intensified' hormone therapy reduces the risk of recurrence
The addition of apalutamide to androgen deprivation therapy clearly improves outcomes in surgical patients: results of the phase 3 Prometeus study
Radical prostatectomy is a potentially curative treatment in people with high-risk, localised or locally advanced prostate cancer; unfortunately, up to half of patients will experience a recurrence within five years. The Proteus trial, a large phase 3 study, presented at the American Society of Clinical Oncology (Asco) congress and published at the same time in the New England Journal of Medicine, looked at whether a new treatment approach could improve outcomes. And its results could indeed change the treatment paradigm for localised high-risk prostate cancer, whose mainstay remains surgery (particularly robotic surgery), assisted by hormone therapy with anti-androgens and radiotherapy.
A new approach
The Proteus study evaluated the efficacy of a new therapeutic approach, i.e. the combination of apalutamide with androgen deprivation therapy, compared with classic hormone deprivation therapy; both therapies were administered both six months before and six months after radical prostatectomy with pelvic lymph node dissection. To evaluate the effectiveness of this new approach, more than 2,000 patients enrolled in 18 countries, including Italia, were involved. After a median follow up of almost 62 months, the percentage of patients with complete pathological response or minimal residual disease was significantly higher in the peri-operative apalutamide-treated group than in the control group (8.9% versus 1%, respectively).
In other words, patients treated with apalutamide prior to surgery were approximately 10 times more likely to have a marked reduction in tumour volume at the time of surgery. Subjects treated with apalutamide also showed a 29% reduction in the risk of tumour recurrence and an increased event-free survival (57.1 months with apalutamide, versus 38.4 months in the control group). The percentage of patients with 5-year metastasis-free survival was also 20% higher in the apalutamide-treated group.
"Our research," explains the study's first author, Dr Mary-Ellen Taplin, of the Dana-Farber Cancer Institute (Boston, USA), "evaluated the effect of 'intensified' androgen deprivation treatment to reduce tumour volume, reclaim any microscopic tumour foci, and improve long-term treatment outcomes. The favourable results obtained in Proteus support the use of apalutamide combined with ADT and radical prostatectomy as a possible new treatment option for patients with localised high-risk prostate cancer'.
Cutting androgens to the tumour
Androgen deprivation therapy (ADT) reduces the production of androgens, hormones that can promote prostate cancer growth. Apalutamide, on the other hand, belongs to the new class of androgen receptor pathway inhibitors (ARPIs); these are drugs that block the action of androgens and, in combination with ADT, further reduce the risk of recurrence or metastasis, as shown in the Proteus study. Patients with high-risk prostate cancer, treated with radical prostatectomy combined with apalutamide and androgen deprivation therapy (ADT), live longer without recurrence or spread of the tumour, compared to subjects treated with surgery and ADT.
Next steps
The researchers' next steps, building on the results of the Proteus study, will be to evaluate the relationship between tumour shrinkage and long-term clinical outcomes; to identify biomarkers that can predict which patients will benefit most from apalutamide; to understand if and when this new treatment may lose efficacy; and to analyse patient-reported outcomes to assess the impact of therapy on quality of life.
