Enzalutamide in mHSPC: Equal efficacy and tolerance after 75 years of age?

10 novembre 2025

By Lila Rouland | Published on November 10, 2025 | 4 min readMetastatic hormone-sensitive prostate cancer (mHSPC) represents a major therapeutic challenge, particularly in older patients who are frequently underrepresented in clinical trials due to comorbidities, physiological frailty, or concerns about increased adverse effects. Yet, over 65% of prostate cancer–related deaths occur in men aged 75

By Lila Rouland | Published on November 10, 2025 | 4 min read

Metastatic hormone-sensitive prostate cancer (mHSPC) represents a major therapeutic challenge, particularly in older patients who are frequently underrepresented in clinical trials due to comorbidities, physiological frailty, or concerns about increased adverse effects. Yet, over 65% of prostate cancer–related deaths occur in men aged 75 years or older, highlighting the need to adapt treatment strategies for this population. The ARCHES study, already known for demonstrating the benefit of enzalutamide combined with androgen deprivation therapy (ADT), presents here a post hoc analysis comparing outcomes in patients younger than 75 versus those aged 75 and older, to determine whether age influences efficacy, safety, and quality of life.

Is enzalutamide equally well tolerated in older patients?

This randomized, double-blind study included 1,150 men with mHSPC, evenly assigned to enzalutamide + ADT or placebo + ADT. Among them, 29.5% were aged 75 or older, and the median follow-up was 44.5 months. The endpoints included overall survival (OS), radiographic progression-free survival (rPFS), adverse events (AEs), and quality-of-life (QoL) parameters.

Patients treated with enzalutamide experienced a significant improvement in overall survival across both age groups.

In patients younger than 75, the hazard ratio (HR) for death was 0.61 (95% CI: 0.47–0.79)
In those aged 75 or older, it was 0.76 (95% CI: 0.54–1.09).

After adjusting for treatment crossover, the survival benefit persisted, with HRs of:

0.54 (95% CI: 0.41–0.71) for the younger group
0.66 (95% CI: 0.44–0.95) for older patients.

Radiographic progression-free survival also favored enzalutamide in both groups, although confidence intervals were broader among older patients due to the smaller sample size.

The treatment was generally well tolerated, though older participants showed higher rates of grade 3–4 adverse events (46.4% vs 36.1%), dose interruptions (20.2% vs 10.9%), and dose reductions (11.9% vs 7.2%). Notably, no treatment-related deaths were reported.

The most common adverse events were fatigue, fractures, falls, and cognitive disturbances, all more frequent among patients aged 75 and older. However, quality-of-life scores (FACT-P) and pain assessments (BPI-SF) remained stable over time, with no significant deterioration, regardless of age.

Age is no longer a barrier to optimal treatment in mHSPC

Metastatic hormone-sensitive prostate cancer, which disproportionately affects older men, demands treatments that are both effective and tolerable. This post hoc analysis of the ARCHES study confirms that enzalutamide combined with ADT significantly improves overall survival and delays disease progression without compromising quality of life, even in patients aged 75 years or older. This holds true despite a more demanding safety profile.

The study’s objective—to assess the impact of age on clinical outcomes—was met: enzalutamide’s efficacy does not decline with age, supporting its use as a standard option at diagnosis, irrespective of age. However, geriatric frailty should be considered through individualized risk–benefit evaluations to optimize patient outcomes.

Future prospective studies focusing specifically on elderly patients are needed to refine clinical decision-making, incorporate frailty assessment tools, and validate these findings in real-world settings.

Read next: Does the circulating tumor cell count predict survival in metastatic hormone-sensitive prostate cancer?

About the author – Lila Rouland

Doctor of Oncology, specialized in Biotechnology and Management

With dual expertise in science and marketing, Lila brings her knowledge to the service of healthcare innovation. After five years in international academic research, she transitioned into medical and scientific communication within the pharmaceutical industry. Now working as a medical writer and content developer, she is committed to highlighting scientific knowledge and conveying it to healthcare professionals with clarity and relevance.

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Scientific reference

Saad, F., et al. (2023). Clinical outcomes of enzalutamide in metastatic hormone-sensitive prostate cancer in patients aged <75 and ≥75 years […]. The Lancet Healthy Longevity, 4(10), e656–e667.

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