Secondary outcomes by prior definitive treatment (tx) in patients (pts) with high-risk biochemically recurrent prostate cancer (hrBCR) treated with enzalutamide (enza) plus leuprolide (combo): EMBARK post hoc analysis.
Authors: Freedland Stephen J. , Gleave Martin , De Giorgi Ugo , Rannikko Antti , Sridharan Swetha , Brasso Klaus , Woo Henry H. , Gómez Caamaño Antonio , Nordquist Luke , Tang Yiyun , Croitoru Ruslan , Rosales Matt , Kalac Matko , Peraud Olivier , Wang Fong , Shore Neal D. 
Published: February 2025

159

Background:
In the phase 3 EMBARK trial, combo vs leuprolide alone meaningfully improved metastasis-free survival (primary endpoint) and secondary efficacy endpoints. Secondary endpoints for combo vs leuprolide alone are reported across prior definitive tx subgroups.
Methods:
EMBARK enrolled pts with hrBCR, defined as a PSA doubling time ≤9 months and PSA ≥1 ng/mL post radical prostatectomy (RP) ± radiotherapy (RT) or ≥2 ng/mL above nadir post RT. Pts were randomized 1:1:1 to combo, leuprolide alone, or enza monotherapy. Secondary endpoints included time to PSA progression, first use of new antineoplastic tx, distant metastasis, resumption of any hormonal therapy after tx suspension, and symptomatic progression. Post hoc subgroup analyses descriptively compared secondary endpoints for combo vs leuprolide alone in pts with prior RP only, RT only, or RP+RT.
Results:
Half of pts in each tx group (combo and leuprolide alone) had prior RP+RT (Table). All secondary endpoints favored combo vs leuprolide alone in all prior definitive tx subgroups (Table). When testing for interactions, there were no statistically significant differences in the observed tx effects for the key secondary endpoints of time to PSA progression (

P
interaction

=0.79) and first use of new antineoplastic tx (

P
interaction

=0.57) across prior definitive tx subgroups. P-interactions for other endpoints will be reported in the presentation.
Conclusions:
Tx with combo showed improvements in all secondary endpoints vs leuprolide alone in all prior definitive tx subgroups, which supports the benefits of combo as the new standard of care for pts with hrBCR regardless of prior definitive tx. The small sample sizes of the non-randomized subgroups and low event numbers should be considered when interpreting results. There were no interactions by prior tx for two key secondary endpoints. Pfizer's generative AI tool, MAIA, was used to draft this abstract (accessed: 2024-10-01); the authors reviewed, edited, and take full responsibility for the content. Clinical trial information:
NCT02319837
.

Secondary endpoints
Combo(n=355)

Leuprolide alone(n=358)
†

RP only(n=90)

RT only
(n=86)

RP+RT
(n=179)

RP only
(n=75)

RT only
(n=104)

RP+RT
(n=179)

Time to:

Events, n

HR
(95% CI)

Events, n

HR
(95% CI)

Events, n

HR
(95% CI)

Events, n

Events, n

Events, n

PSA progression
1
0.05(0.01, 0.41)
4
0.10(0.03, 0.27)
3
0.06(0.02, 0.21)
17
37
39

First use of new antineoplastic tx
16
0.54(0.28, 1.02)
15
0.28(0.15, 0.52)
27
0.34(0.21, 0.53)
25
48
67

Distant metastasis
5
0.51(0.17, 1.59)
12
0.47(0.22, 1.00)
13
0.34(0.18, 0.67)
9
20
30

Resumption of any hormonal therapy
69
0.74(0.51, 1.08)
64
0.92(0.61, 1.39)
123
0.60(0.46, 0.79)
54
47
116

Symptomatic progression
29
0.76(0.46, 1.28)
27
0.55(0.34, 0.89)
48
0.46(0.32, 0.66)
32
52
85

†
Leuprolide alone was the comparator.