XTANDI Shows Long-Term Overall Survival Benefit in Metastatic Hormone-Sensitive Prostate Cancer

Analysis reveals significant industry trends and economic implications

Release Date

2025-05-23

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Five-year follow-up data from the Phase 3 ARCHES trial (NCT02677896) demonstrates that XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) significantly reduces the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC). The study showed a 30% reduction in the risk of death and a 66% probability of survival at five years with XTANDI plus ADT compared to 53% with placebo plus ADT. Benefits were observed across various patient subgroups, including those with high-volume disease. These findings reinforce XTANDI plus ADT as a standard of care for mHSPC. Eight-year data from the ENZAMET study (NCT02446405) further supports these long-term benefits.

Key Highlights

  • XTANDI plus ADT reduced the risk of death by 30% in men with mHSPC in the ARCHES trial.
  • 66% probability of survival at five years observed with XTANDI plus ADT compared to 53% with placebo plus ADT.
  • Benefits seen across various patient subgroups, including those with high-volume disease.
  • Eight-year data from the ENZAMET study also showed sustained survival benefits with XTANDI.

Incidence and Prevalence

Global Incidence and Prevalence of Metastatic Hormone-Sensitive Prostate Cancer

Prostate carcinoma (PC) ranks as the second most diagnosed cancer globally, with approximately 1,414,000 new cases reported in 2020. The global burden of metastatic hormone-sensitive prostate cancer (mHSPC) represents a significant portion of these cases.

Incidence

  • 17% of prostate cancer cases are de novo metastatic (metastatic at initial diagnosis)
  • De novo metastatic castration sensitive prostate cancer (mCSPC) accounts for about 4% of all prostate tumors in Western Countries
  • In the United States, 1 in 8 men will be diagnosed with prostate cancer in their lifetime

Disease Characteristics

mHSPC includes patients with: - Metastatic disease at initial diagnosis - Metastatic disease after initial therapy without long-term androgen deprivation therapy

The clinical and biological behavior of mHSPC is notably heterogeneous, with presentation ranging from indolent forms to aggressive and rapidly fatal manifestations.

Survival

For patients with metastatic prostate cancer, the 5-year relative survival rate is 32%, highlighting the significant mortality associated with advanced disease.

Global Impact

Prostate cancer continues to be one of the most commonly diagnosed cancers in men globally and remains a leading cause of male cancer deaths.

This data underscores the significant global health burden of metastatic hormone-sensitive prostate cancer and the importance of early detection and effective treatment strategies.

Emerging Mechanism of Action

Emerging Mechanisms of Action for Metastatic Hormone-Sensitive Prostate Cancer

Recent publications in PubMed over the past three years highlight several key mechanisms of action emerging for metastatic hormone-sensitive prostate cancer (mHSPC) treatment.

Current Backbone Treatment

Androgen Deprivation Therapy (ADT) remains the foundation of mHSPC treatment but is now being significantly enhanced with various combination approaches to improve outcomes.

Key Emerging Mechanisms

Androgen Receptor Pathway Inhibitors (ARPI)

These agents have demonstrated significant efficacy in recent studies: - Abiraterone acetate (combined with prednisone) has proven effective in both mHSPC and castration-resistant prostate cancer - Next-generation antiandrogens including enzalutamide, apalutamide, and darolutamide show promising results - Rezvilutamide, a newer ARPI, is demonstrating effectiveness in clinical settings

Effective Treatment Combinations

Several combination approaches are showing superior outcomes: - ADT + docetaxel demonstrated an overall survival benefit of 13.6 months compared to ADT alone in the CHAARTED trial - ADT + abiraterone has proven highly beneficial for mHSPC treatment - "Triplet therapy" combining ARPI + docetaxel + ADT showed improved overall survival (HR 0.74; 95% CI, 0.66-0.83, p < 0.00001) - Particularly significant benefits have been observed for high-volume mHSPC (HR 0.76) and de novo metastatic disease (HR 0.73)

Novel Approaches Under Investigation

Current research is exploring several innovative treatment strategies: - Local cytoreductive treatments and metastasis-directed therapy - PI3K pathway inhibitors - DNA damage response inhibitors - Targeted alpha therapy - PSMA (prostate-specific membrane antigen) targeting approaches - Immune checkpoint inhibitors (though these have shown limited benefits thus far)

Clinical Decision-Making Considerations

Treatment selection is becoming increasingly nuanced: - Patient selection for specific therapies is growing in importance - No head-to-head studies currently indicate superiority of one agent over others - Sequencing of hormonal therapies, chemotherapies, and immunotherapies has not yet been standardized

The field of mHSPC treatment is rapidly evolving, with combination approaches showing the most promise for improving patient outcomes. The integration of novel targeted therapies alongside established treatments represents a significant advancement in managing this challenging disease.

Drug used in other indications

XTANDI (enzalutamide) and ADT Trial Indications and Intervention Models

XTANDI (enzalutamide) and androgen deprivation therapy (ADT) have been studied in several indications beyond metastatic hormone-sensitive prostate cancer (mHSPC), including:

  • Metastatic castration-resistant prostate cancer (mCRPC)
  • Nonmetastatic castration-resistant prostate cancer (nmCRPC)

Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)

For nmCRPC, enzalutamide has demonstrated significant clinical benefits: - Enzalutamide has been approved for the treatment of nmCRPC - An improvement in metastasis-free survival (MFS) was observed with enzalutamide use - Recently released preliminary data also report an overall survival (OS) benefit

Intervention Models

The intervention model described for the ARCHES trial (which studied enzalutamide in mHSPC) was: - A multinational, double-blind, phase III trial - 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus ADT - Stratified by disease volume and prior docetaxel chemotherapy - The primary endpoint was radiographic progression-free survival

Additionally, other trials with similar agents were conducted, such as the ARASENS trial, which studied darolutamide with ADT and docetaxel in mHSPC patients.