Secondary outcomes by prior definitive treatment (tx) in patients (pts) with high-risk biochemically recurrent prostate cancer (hrBCR) treated with enzalutamide (enza) monotherapy (mono): EMBARK post hoc analysis.
Authors: Freedland Stephen J. , De Giorgi Ugo , Tutrone Ronald F. , Karsh Lawrence Ivan , Ramirez-Backhaus Miguel , Uchio Edward M. , Tang Yiyun , Croitoru Ruslan , Rosales Matt , Kalac Matko , Wang Fong , Shore Neal D. 
Published: February 2025

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Background:
The phase 3 EMBARK trial demonstrated clinically meaningful improvement in metastasis-free survival and secondary efficacy endpoints with enza mono vs leuprolide alone. Herein, we descriptively report secondary endpoints for enza mono vs leuprolide alone across prior definitive tx subgroups.
Methods:
Eligible pts had hrBCR, with a prostate-specific antigen (PSA) doubling time ≤9 months. Pts were randomized 1:1:1 to enza + leuprolide, leuprolide alone, or enza mono. 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 enza mono vs leuprolide alone in pts with radical prostatectomy (RP) only, radiotherapy (RT) only, or RP+RT.
Results:
In both tx groups (enza mono and leuprolide alone), nearly half of pts had prior RP+RT (Table). Enza mono vs leuprolide alone numerically reduced the risk of PSA progression, first use of new antineoplastic tx, distant metastasis, and symptomatic progression in all prior definitive tx subgroups (Table). Time to resumption of any hormonal therapy favored leuprolide alone vs enza mono across all prior definitive tx subgroups.
Conclusions:
Tx with enza mono showed improvements in all secondary endpoints except time to resumption of any hormonal therapy vs leuprolide alone, regardless of prior definitive tx. The small sample sizes of the non-randomized prior tx subgroups and low event numbers should be considered when interpreting the results. Interaction analyses of secondary endpoints across prior definitive tx subgroups will be reported in the presentation. 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
Mono (n=355)

Leuprolide alone(n=358)
†

RP only (n=99)

RT only (n=90)

RP+RT (n=166)

RP only (n=75)

RT only (n=104)

RP+RT (n=179)

Time to:

Event, n

HR (95% CI)

Event, n

HR (95% CI)

Event, n

HR (95% CI)

Event, n

Event, n

Event, n

PSA progression
12
0.62 (0.28, 1.34)
18
0.53 (0.30, 0.95)
7
0.14 (0.06, 0.33)
17
37
39

First use of new antineoplastic tx
23
0.68 (0.38, 1.22)
33
0.76 (0.48, 1.20)
28
0.37 (0.23, 0.58)
25
48
67

Distant metastasis
10
0.81 (0.32, 2.08)
14
0.65 (0.31, 1.34)
16
0.45 (0.24, 0.85)
9
20
30

Resumption of any hormonal therapy
77
1.68 (1.14, 2.46)
60
2.23 (1.46, 3.39)
142
1.58 (1.22, 2.03)
54
47
116

Symptomatic progression
28
0.61 (0.36, 1.03)
38
0.79 (0.52, 1.22)
51
0.56 (0.39, 0.80)
32
52
85

†
Leuprolide alone was the comparator.