Results from the ARCHES study, presented at the European Society for Medical Oncology (ESMO) Congress 2021, showed an improved overall survival (OS) men with metastatic hormone-sensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer).

The Phase 3, randomised, double-blind, placebo-controlled trial compared enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in men with mHSPC and OS was a key secondary endpoint.

In the study, enzalutamide plus ADT reduced the risk of death by 34% (n=1,150; hazard ratio [HR]=0.66; [95% confidence interval [CI]: 0.53-0.81]; p<0.0001) compared to placebo plus ADT.

Median OS, which represents the time from randomisation to death due to any cause, was not reached in either treatment group.

The safety profile in both study arms was consistent with findings from the primary analysis.

Results from the final analysis of the ARCHES trial were presented virtually at ESMO by Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, and Director of Research in the Duke Cancer Institute's Center for Prostate and Urologic Cancers in Durham, North Carolina, U.S. (Abstract LBA25; September 18, 14:20 CEST).

"Overall survival benefit has been observed in patients treated with enzalutamide in three stages of advanced prostate cancer – metastatic castration-resistant prostate cancer, non-metastatic castration-resistant prostate cancer, and now in metastatic hormone-sensitive prostate cancer," said Dr. Armstrong. "The results from ARCHES provide valuable data on the clinical profile of enzalutamide in this earlier disease setting."

The primary results from the ARCHES trial were published in the Journal of Clinical Oncology in 2019.

The study met its primary endpoint of radiographic progression-free survival (rPFS) as assessed by independent central review, finding that treatment with enzalutamide plus ADT demonstrated a 61% reduction in the risk of radiographic disease progression or death compared with ADT alone in men with mHSPC (HR=0.39; [95% CI: 0.30-0.50]; p<0.001).

The median follow-up time was 14.4 months. Median rPFS was not reached (NR) with enzalutamide plus ADT (95% CI: NR to NR) versus 19.0 months (95% CI: 16.6-22.2 months) with placebo plus ADT. At the time of the primary analysis, OS data were not mature.

In the ARCHES primary analysis, Grade 3 or greater adverse events (AEs; defined as severe/disabling or life-threatening) were similar for patients receiving both enzalutamide plus ADT and those who received placebo plus ADT (24.3% vs. 25.6%).

Common AEs (occurring in at least 5% of patients) that were reported more often in patients treated with enzalutamide plus ADT versus those treated with ADT alone included hot flush, fatigue, arthralgia, hypertension, nausea, musculoskeletal pain, diarrhoea, asthenia and dizziness.

These data supported global regulatory approvals, including European Commission marketing authorisation for mHSPC earlier this year.

Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as the lymph nodes, bones, lungs, and liver.

Men are considered hormone- (or castration-) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.

Metastatic hormone-sensitive prostate cancer (mHSPC) has a median survival of approximately 3-4 years for men starting treatment with ADT.

The company-sponsored, Phase 3, randomised, double-blind, placebo-controlled ARCHES trial (NCT02677896) enrolled 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region.

Patients in the trial were randomised to receive enzalutamide 160 mg daily or placebo and continued on a luteinising hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy.

The primary endpoint of the trial was radiographic progression-free survival (rPFS) assessed by blinded independent central review.

Radiographic progression-free survival was defined as the time from randomisation to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation.

Radiographic disease progression was defined by identification of two or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease.

Patients were stratified by volume of disease (low vs. high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles).

Watch ecancer's interview with Prof Andrew Armstrong on this study here.

Source: Astellas Pharma Inc. / Pfizer Inc.