Enzalutamide plus ADT shows efficacy in men with CSPC with bone, soft tissue metastases

The combination of enzalutamide (Xtandi) and androgen deprivation therapy (ADT) appears to be beneficial in patients with oligometastatic and polymetastatic castration-sensitive prostate cancer (CSPC), regardless of whether the patient has bone, soft tissue, or both types of metastases, according to research presented at the 2021 Society of Urologic Oncology Annual Meeting.¹

Andrew J. Armstrong, MD

The data, derived from the ARCHES trial (NCT02677896), were presented by investigator Andrew J. Armstrong, MD, MSc, a medical oncologist at Duke Cancer Center, Durham, North Carolina.

Investigators previously reported that enzalutamide plus ADT provided clinical benefit for patients with oligometastatic and polymetastatic CSPC with bone-only metastases; however, that analysis excluded patients with soft tissue disease.² In addition, overall survival (OS) data were immature at the time of the analysis and could not be examined.

The objective of the current analysis was to evaluate the effect of enzalutamide plus ADT vs placebo plus ADT in patients with mCSPC with bone, soft tissue, or both types of metastases, categorized as either oligometastatic (1 to 5 or fewer metastases) or polymetastatic (6 or more metastases). Patients were categorized as oligometastatic or polymetastatic based on central review of MRI, CT, or radionuclide bone scans at screening.

A total of 1150 patients with mCSPC were randomized 1:1 to receive enzalutamide (160 mg/day) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use.

Efficacy outcomes were compared for patients on enzalutamide plus ADT vs placebo plus ADT within the defined groups and against polymetastatic disease.

The primary end point was radiographic progression-free survival (rPFS), with secondary end points of OS, time to prostate-specific antigen (PSA) progression, time to castration resistance, time to first symptomatic skeletal event, time to initiation of new antineoplastic therapy, and PSA undetectable rate. Kaplan Meier estimates were used to analyze primary time-to-event end point of rPFS, and a 2-sided 95% CI for median time was estimated using the Brookmeyer and Crowley method. Hazard ratios were estimated from the Cox proportional hazards model. Investigators performed similar analyses for selected secondary time-to-event end points.

Armstrong noted differences in several baseline characteristics between patients with oligometastatic and polymetastatic disease: Men with polymetastatic disease were more likely to have metastatic disease at study entry, had higher PSA levels, were more likely to have visceral disease, and they were less likely to have been previously treated with radical prostatectomy or radiation therapy.

Discussing the results of the study, Armstrong said, “The efficacy of enzalutamide is very clearly beneficial in all these subgroups, with hazard ratios ranging from .26 to .46, with no heterogeneity between these effect sizes.”

He added, “For the extended overall survival results, the hazard ratios are nearly identical at around 0.62, with efficacy even being seen in patients with 1-2 bone metastases or soft tissue metastases.”

Armstrong also reported improvements in time to PSA progression, time to castration resistance, time to first symptomatic skeletal event, and time to initiation of new antineoplastic therapy, with benefits seen regardless of the number of metastases.

Regarding adverse events, Armstrong said, “The side effects with enzalutamide were really not all that different in the polymetastatic vs oligometastatic disease, with no unexpected findings as compared with the overall ARCHES population. Notably, perhaps, fatigue was slightly increased in the oligometastatic patients, perhaps because of the longer duration of treatment that these patients received.”

In his concluding remarks, Armstrong said, “This post hoc analysis demonstrates that enzalutamide plus ADT provides clear clinical benefits in improving survival, delaying progression, and other secondary end points in patients with oligometastatic disease and really no heterogeneity of outcomes based on the number of conventional imaging sites. These results validate and support the overall findings of ARCHES.”

References

1. Armstrong AJ, Holzbeierlein J, Iguchi T, et al. The efficacy of enzalutamide plus androgen deprivation therapy on oligometastatic hormone-sensitive prostate cancer: Extended post hoc analysis of ARCHES. Paper presented at: 2021 Society of Urologic Oncology Annual Meeting; December 1-3, 2021; Orlando, Florida. Abstract 62

2. Armstrong AJ, Iguchi T, Azad A, et al. The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. J Clin Oncol. 2021;39, no. 15_suppl (May 20, 2021) 5071-5071. doi:10.1200/JCO.2021.39.15_suppl.5071