AUA 2019: ARCHES – Efficacy of ADT with Enzalutamide or Placebo in Metastatic Hormone-sensitive Prostate Cancer: PSA Results

Chicago, IL (UroToday.com) Dr. Stenzl presented the PSA results of the ARCHES trial – which was a randomized controlled phase three trial, that assessed the efficacy of androgen deprivation (ADT) with enzalutamide or placebo in metastatic hormone-sensitive prostate cancer (mHSPC) patients.

Enzalutamide is a potent androgen receptor inhibitor, demonstrating clinical benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). The ARCHES study assessed the efficacy and safety of enzalutamide in combination with ADT in another unique setting - men with mHSPC. The baseline PSA level is still considered to be a strong prognostic factor for clinical outcomes in patients with mHSPC following ADT. In this presentation, Dr. Stenzl reported the PSA-related primary and secondary endpoints in the ARCHES trial (design shown in figure 1).

Figure 1- ARCHES study design:

The primary endpoint of the study included radiographic progression-free survival (rPFS) (defined as the time from randomization to the first objective evidence of radiographic disease progression, as assessed by independent central review), or death from any cause within 24 weeks of treatment discontinuation, (whichever occurred first). The key secondary endpoints included time to PSA progression, and PSA undetectable rate (<0.2 ng/ml). Other secondary endpoints included time to castration resistance, PSA reductions from baseline, and safety. The statistical design included a target of 262 progression events, with a power of 90%, to detect a hazard ratio of 0.67 (assuming a median rPFS of 20 months with placebo). The baseline patient characteristics of the 1,150 patients that were analyzed are shown in table 1.

Table 1 – Baseline patient characteristics:

The rPFS for the overall population in the trial arms is shown in figure 1, and the rPFS by baseline PSA is shown in figure 2. The secondary endpoint of time to PSA progression and time to castration resistance are shown in figure 3. In all primary and secondary endpoints enzalutamide +ADT conferred a significant advantage compared to placebo + ADT. Patients in the enzalutamide +ADT arm achieved a greater decline in PSA from baseline to day 29 than patients in the placebo +ADT arm achieved during the entire treatment period. Lastly, the PSA undetectable rate is shown in figure 4, again demonstrating a significant higher percentage of patients with undetectable PSA in the enzalutamide +ADT arm.

Figure 1 – Radiographic progression-free survival for the entire study population:

Figure 2 – Radiographic progression-free survival by baseline PSA:

Figure 3 – Secondary endpoints:

Figure 4 – PSA undetectable rate:

The most commonly encountered adverse events (occurring >=5% of patients) in either group included hot flushes, fatigue, arthralgia, back pain, increased weight, hypertension, diarrhea, peripheral edema, nausea, asthenia, constipation, dizziness, and musculoskeletal pain.

Dr. Stenzl concluded his talk on this important study, stating that enzalutamide + ADT significantly improve rPFS compared to the placebo +ADT arm in the overall population. Enzalutamide + ADT also significantly improved rPFS than that demonstrated in the placebo +ADT arm, regardless of baseline PSA level at study entry. Additionally, enzalutamide and ADT also improved other endpoints, further supporting clinical benefit of this intervention in men with mHSPC. These other endpoints included time to PSA progression, time to castration resistance, PSA reduction from baseline, and PSA undetectable rate. Lastly, preliminary safety analysis appears consistent with the safety profile of enzalutamide in previous CRPC trials.

Presented by: Professor Arnulf Stenzl, MD, Department of Urology, University of Tuebingen, Germany

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois

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