Predictors of treatment (tx) duration in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (ENZA): A post hoc analysis of ARCHES.

Abstract

5093 Background: In ARCHES (NCT02677896), ENZA + androgen-deprivation therapy (ADT) significantly improved radiographic progression-free survival (primary: data cutoff, Oct 14, 2018) and overall survival (prespecified secondary: data cutoff, May 28, 2021; 5-year follow-up: data cutoff, Jul 31, 2024) vs placebo + ADT in mHSPC. This post hoc analysis explored factors associated with different ENZA tx durations (5-year follow-up). Methods: Reasons for tx discontinuation (DC) including toxicity and progression, and baseline and on-treatment factors underlying tx persistence, were compared descriptively among pts with short (0–2 years [y]; STx), medium (2–5 y; MTx), and long Tx duration (> 5 y; LTx) (STx pts represent non-responders; MTx/LTx pts represent tx responders). Results: Of 572 ENZA-treated pts, 204 (36%) were STx; 140 (24%) MTx; 228 (40%) LTx. STx pts were more likely to be older vs MTx and LTx, with high-volume disease (HVD) and Eastern Cooperative Oncology Group performance status (ECOG PS) 1, although 55.3% of LTx had HVD and 73.2% had synchronous metastases. Progressive disease and tx-emergent adverse events (TEAEs) were the most common reasons for tx DC. Drug-related TEAEs (per 100 pt-y) were more common in STx (156.0) vs MTx (89.5) and LTx (47.1), as were those leading to tx DC (STx: 12.4; MTx: 1.5; LTx: 0.1). Rates (per 100 pt-y) of TEAEs leading to ENZA dose reduction were higher in STx (6.2) vs MTx (5.8) and LTx (2.0). The rate (per 100 pt-y) of drug-related TEAEs of special interest were generally higher in STx vs MTx and LTx: convulsions (1.0 vs 0.0 vs 0.0); fatigue (19.0 vs 10.7 vs 4.8), select cardiovascular events (1.0 vs 0.6 vs 0.1); falls (2.4 vs 3.2 vs 1.1); fractures (0.5 vs 1.5 vs 0.5). Conclusions: Our findings demonstrate that LTx and MTx tended to have more favorable pt and disease characteristics vs STx, although majority of LTx had adverse prognostic features. While progressive disease was the most common reason for DC, AEs/withdrawals were the second most common. Most TEAEs of special interest were more frequent in STx. Reasons for AE-related tx changes are multifactorial, and optimal management of AEs and comorbidities, as well as dose modifications, can optimize ENZA tx. Clinical trial information: NCT02677896 . Pt characteristics STx (n = 204)n (%) MTx (n = 140)n (%) LTx (n = 228)n (%) Age: ≥ 18 to 64/≥ 65 to ≤ 84/≥ 85 y 45 (22.1)/150 (73.5)/9 (4.4) 38 (27.1)/100 (71.4)/2 (1.4) 65 (28.5)/159 (69.7)/4 (1.8) Prostate-specific antigen nadir < 0.2 ng/mL post-baseline 84/189 (44.4) 97/123 (78.9) 181/198 (91.4) ECOG PS 0/1 147 (72.1)/57 (27.9) 110 (78.6)/30 (21.4) 190 (83.3)/37 (16.2) HVD 148 (72.5) 80 (57.1) 126 (55.3) Synchronous disease 162 (79.4) 108 (77.1) 167 (73.2) Reasons for tx DC Progressive disease 106 (52.0) 63 (45.0) 19 (8.3) AE + withdrawalAEWithdrawal 74 (36.3)40 (19.6)34 (16.7) 40 (28.6)25 (17.9)15 (10.7) 7 (3.1)2 (0.9)5 (2.2) Death 10 (4.9) 10 (7.1) 10 (4.4)