Clinical Benefit of Enzalutamide Is Elucidated in Oligometastatic Hormone-Sensitive Prostate Cancer

The combination of enzalutamide (Xtandi) and androgen deprivation therapy (ADT) provided a clinical benefit compared with placebo in patients with oligometastatic and polymetastatic hormonesensitive prostate cancer (HSPC) with bone, soft tissue, or both types of metastatic involvement, according to a post hoc analysis of the ARCHES study (NCT02677896). Findings were presented by lead study author Andrew J. Armstrong, MD, MSc, during the 22nd Annual Meeting of the Society of Urologic Oncology.¹ In previous studies, including the primary analysis of ARCHES, patients with bone-only oligometastatic involvement were evaluated. These current findings validate and support the clinical utility of enzalutamide regardless of metastatic burden or type of oligometastatic disease, according to the investigators.

Enzalutamide and ADT reduced the risk of radiographic progression vs placebo and ADT across all oligometastatic groups (HRs, 0.26-0.46) and improved overall survival (HRs, 0.60-0.63). An improvement in radiographic progression-free survival (rPFS) in patients with the most oligometastatic metastases (≤5) of 66% was observed in the enzalutamide and ADT group compared with placebo and ADT (HR, 0.34; 95% CI, 0.22-0.55). Similarly, an improvement of 40% was observed for overall survival (OS) in the enzalutamide and ADT group vs the placebo and ADT group (HR, 0.60; 95% CI, 0.42-0.86).

Enzalutamide and ADT reduced the risk of radiographic progression by 62% vs placebo and ADT in patients with polymetastatic disease (HR, 0.38; 95%, 0.28-0.52) and reduced the risk of death by 37% (HR, 0.63; 95% CI, 0.48-0.82).

Investigators reported that patients with oligometastatic disease exhibited a better prognosis than those with polymetastatic disease in both groups, regardless of the number of metastatic lesions. For patients with 6 or more metastases, HRs for rPFS ranged from 0.14 to 0.37 for the treatment group and 0.21 to 0.40 for the control group. HRs for OS were 0.26 to 0.40 in the treatment group and 0.25 to 0.40 in the control group.

Oligometastatic disease has become more relevant for prostate cancer management.

Treatments for oligometastatic disease include metastasis-directed radiation or surgery, ADT combined with androgen receptor inhibition, or ADT alone. The optimal treatment approach, however, has yet to be identified.

In the ARCHES trial, 1150 patients with metastatic HSPC were randomized 1:1 to receive enzalutamide at 160 mg/day and ADT or placebo and ADT, stratified by disease volume and prior docetaxel use. Investigators noted that enzalutamide and ADT significantly reduced the risk of radiographic progression by 61% (P <.001), with an improvement in secondary end points. After a median follow-up of 44.6 months, enzalutamide and ADT improved OS by 34% (P <.0001); median OS was not reached in either treatment group.²

Primary end points were rPFS, and secondary end points were OS and time to prostatespecific antigen (PSA) progression.

Baseline characteristics were generally comparable between treatment arms; however, there were some differences across the subgroups for baseline PSA, distant metastases at initial diagnosis, Gleason score, and other prognostic variables (TABLE).

Patients with oligometastatic disease who were treated with enzalutamide and ADT had slightly higher rates of treatment-emergent adverse events (TEAEs; 90.7% vs 85.5%), similar rates of grade 3/4 TEAEs (20.9% vs 22.9%), but fewer serious TEAEs (14.6% vs 19.7%). Investigators noted that in the polymetastatic disease group, lower rates of TEAEs were observed for the treatment group compared with the placebo group (80.4% vs 86.8%). Further, a similar rate of grade 3/4 TEAEs (26.0% vs 27.4%), but slightly more serious TEAEs were observed in the treatment group vs the placebo group (22.6% vs 20.3%).

_REFERENCES

_{1. Armstrong AJ, Holzbeierlein J, Iguchi T, et al. The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on oligometastatic hormone-sensitive prostate cancer: extended post hoc analysis of ARCHES. Presented at: 22nd Annual Meeting of the Society of Urologic Oncology; December 1-3, 2021; Orlando, FL. Accessed December 15, 2021. https://bit.ly/323rbUu}

_{2. Armstrong AJ, Iguchi T, Azad AA, et al. Final overall survival (OS) analysis from ARCHES: a phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). Ann Oncol. 2021;32(suppl 5): S1300-1301. doi: 10.1016/annonc/annonc741}