Subgroup data sustain enzalutamide PFS benefit in nmCRPC

No new safety signals were reported with the androgen receptor pathway inhibitor.

Subgroup data from the phase 2 STRIVE trial shared during the 2020 Society of Urologic Oncology Annual Meeting upheld the progression-free survival (PFS) benefit with enzalutamide (Xtandi) over bicalutamide (Casodex) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) shown in the primary study results.1

The subgroups analysis from the STRIVE study also showed that treatment with enzalutamide was associated with an increased time to prostate-specific antigen (PSA) progression (TTPP) compared with bicalutamide

Bicalutamide is still commonly used as treatment of patients with nmCRPC in many parts of the world, but evidence has shown improvements in survival with the use of enzalutamide instead. The risk of prostate cancer progression or death was significantly reduced with enzalutamide compared with bicalutamide (HR, 0.24; 95% CI, 0.18-0.32; P <.001) as treatment of patients with CRPC who had either nonmetastatic or metastatic disease in the overall results of the STRIVE trial.2 The purpose of the prespecified subgroup analysis was to determine the clinical benefit of this therapy over bicalutamide as treatment of patients with nmCRPC specifically.

Patients enrolled in STRIVE were stratified by disease stage of either nmCRPC or mCRPC and were randomized to receive either 160 mg/day enzalutamide plus androgen deprivation therapy (ADT) or bicalutamide at 50 mg/day plus ADT. Overall, 128 men with mCRPC and 70 with nmCRPC were included in the enzalutamide arm, while 129 and 69, respectively, were allocated to the control arm. The subgroup analysis included 139 men with nmCRPC who were assessed for PFS, time to PSA progression, and safety.

At baseline, the demographics and patient characteristics were generally well balanced between the 2 treatment arms. The median age of patients with 77.0 years in the bicalutamide arm versus 73.5 years in the enzalutamide arm, and the control group had a longer PSA doubling time as well, with a median of 5.3 months versus 3.9 months, respectively. The majority of patients were Caucasian in the enzalutamide and control arms (75.7% vs 84.1%, respectively), had an ECOG performance status of 0 (80.0% vs 76.8%), and had node-negative disease at study entry (87.1% vs 87.0%).

Among patients with nmCRPC in the STRIVE study, the median PFS with enzalutamide was not reached (NR; 95% CI, 19.4-NR) versus 8.6 months (95% CI, 8.1-11.1) in the control arm (HR, 0.24; 95% CI, 0.14-0.42). The median TTPP was also NR in the enzalutamide arm (95% CI, NR-NR) versus 11.1 months (95% CI< 8.4-13.9) in the control arm (HR, 0.18; 95% CI, 0.10-0.34).

Enzalutamide reduced the risk of progression or death by 76% at a median follow-up of 17 months, and achieved an 82% reduction in the risk of PSA progression, compared with the bicalutamide arm.

Although the PFS benefit was consistent across all subgroups examined, the benefit did not reach statistical significance among those with a PSA doubling time ≥12 months (HR, 0.26; 95% CI, 0.03-2.39).

The median PFS was not reached for several subgroups in the enzalutamide arm, but among those that were reached, the median PFS with enzalutamide was 16.7 months versus 8.5 months in the control (HR, 0.29; 95% CI, 0.13 to 0.62) for those with a total Gleason score at diagnosis of≥8, 19.0 versus 5.6 months (HR, 0.22; 95% CI, 0.10-0.49) for those with a baseline PSA value above 7.42 ng/mL, and 19.4 versus 8.1 months (HR, 0.23; 95% CI, 0.09-0.58) for those with a PSA doubling time of less than 3 months, respectively.

A sensitivity analysis based on different censoring rules for the population of patients with nmCRPC did not appear to affect the PFS benefit of enzalutamide compared with bicalutamide. In an analysis of the impact of censoring due to unconfirmed progressive disease, the median PFS was NR in the enzalutamide arm (95% CI, 19.0-NR) versus 8.6 months (95% CI, 8.1-11.1) in the control (HR, 0.26; 95% CI, 0.15-0.43; P <.0001), and in an analysis censoring due to treatment discontinuation, the median PFS was 19.4 months (95% CI, 14.1-NR) versus 8.5 months (95% CI, 5.9-11.1), respectively (HR, 0.40; 95% CI, 0.26-0.62; P <.0001).

The analysis of the impact of censoring due to prostate cancer therapies showed a median PFS of NR (95% CI, 19.4-NR) with enzalutamide versus 8.6 months (95% CI, 8.1-11.1) in the control group (HR, 0.24; 95% CI, 0.14-0.42; P <.0001). The sensitivity analysis of the impact of censoring due to disease progression at an unscheduled visit demonstrated a median PFS that was NR in the experimental arm (95% CI, 19.4-NR) versus 8.6 months (95% CI, 8.1-11.1) in the control arm (HR, 0.24; 95% CI, 0.14-0.42; P <.0001).

Patients in the enzalutamide arm had a longer median time on treatment at 17.8 months compared with 12.3 months in the control arm. The proportion of patients with at least 1 adverse event (AE) was similar among those with nmCRPC and those with mCRPC, occurring in 92.8% versus 93.8%, respectively. However, the proportion of patients with at least 1 AE was higher in the mCRPC arm (92.2%) than the nmCRPC arm (84.1%) in those treated with bicalutamide.

The most common treatment-emergent AEs (TEAEs), unadjusted for treatment exposure, included fatigue (36.2% with enzalutamide vs 21.7% with bicalutamide, respectively), hot flash (20.3% vs 2.9%), decreased appetite (17.4% vs 5.8%), dizziness (17.4% vs 4.3%), and nausea (17.4% vs 13.0%) among the men included in the nmCRPC subgroup analysis.

Grade 3 or higher TEAEs occurred in 42.0% of patients in the enzalutamide arm versus 37.7% of the control arm. The most common grade 3 or higher TEAEs in the enzalutamide arm included fatigue in 5.8% compared with 2.9% in the control arm, arthralgia in 4.3% versus 1.4%, congestive cardiac failure in 4.3% versus 1.4%, and hypertension in 4.3% versus 2.9%.

References

1. Penson DF, Armstrong AJ, Concepcion RS, et al. Enzalutamide (ENZA) versus bicalutamide (BIC) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a prespecified subgroup analysis of the STRIVE trial. Presented at: 2020 SUO Annual Meeting; December 2-5, 2020; Virtual. Abstract 133.

2. Penson DF, Armstrong AJ, Concepcion R, et al. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016;34:2098-2106. doi: 10.1200/JCO.2015.64.9285