Are long-term remissions possible with hormonal therapy only? Post hoc analysis of EMBARK examining sustained prostate-specific antigen (PSA) <0.2 ng/mL despite testosterone (T) recovery after treatment (tx) suspension.

Abstract

189 Background: The phase 3 EMBARK trial (NCT02319837) assessed enzalutamide plus leuprolide (enza combo), leuprolide alone (LA), and enzalutamide monotherapy (enza mono) in patients (pts) with prostate cancer and high-risk biochemical recurrence. EMBARK demonstrated significant improvements for metastasis-free survival (enza combo and enza mono) and overall survival (enza combo). A key feature of EMBARK was tx suspension after 37 weeks in pts with PSA <0.2 ng/mL. We assessed the proportion of pts with sustained PSA <0.2 ng/mL despite T recovery. Methods: Pts were randomized 1:1:1 to receive enza combo, LA, or enza mono. Pts received tx for 36 weeks. This post hoc analysis evaluated proportions of pts with PSA <0.2 ng/mL and T recovery to baseline, 175 ng/dL, or 250 ng/dL after tx suspension of 12, 24, or 36 months. Results: During the entire 36 months after tx suspension, 9.3%, 3.4%, and 2.3% of pts in the enza combo (n=353), LA (n=354), and enza mono groups (n=354), respectively, maintained PSA <0.2 ng/mL; proportions during 12 and 24 months are shown (Table). During 36 months after tx suspension, among pts in the enza combo, LA, and enza mono groups, respectively, 3.7%, 1.4%, and 1.1% maintained PSA <0.2 ng/mL and achieved T recovery to >250 ng/dL. Results for T recovery to baseline and >175 ng/dL are shown (Table). Conclusions: Approximately 1 in 25 pts treated with enza combo for 9 months had PSA <0.2 ng/mL and normal T 3 years post therapy, demonstrating long-term “remissions” are possible after only 9 months of enza combo. Rates with LA and enza mono were not zero but were much lower than with enza combo (both 1%, vs 4% with enza combo). Clinical trial information: NCT02319837 . Pts with PSA <0.2 ng/mL and T recovery after tx suspension (safety population). 12 months 24 months 36 months Enza combo (n=353) LA (n=354) Enza mono (n=354) Enza combo (n=353) LA (n=354) Enza mono (n=354) Enza combo (n=353) LA (n=354) Enza mono (n=354) Pts with PSA <0.2 ng/mL during suspension, n (%) 127 (36.0) 53 (15.0) 33 (9.3) 58 (16.4) 24 (6.8) 15 (4.2) 33 (9.3) 12 (3.4) 8 (2.3) T >175 ng/dL † , n (%) 72 (20.4) 33 (9.3) 29 (8.2) 35 (9.9) 17 (4.8) 12 (3.4) 15 (4.2) 8 (2.3) 5 (1.4) T >250 ng/dL ‡ , n (%) 44 (12.5) 21 (5.9) 23 (6.5) 25 (7.1) 15 (4.2) 10 (2.8) 13 (3.7) 5 (1.4) 4 (1.1) T ≥baseline § , n (%) 21 (5.9) 11 (3.1) 18 (5.1) 16 (4.5) 10 (2.8) 10 (2.8) 9 (2.5) 3 (0.8) 4 (1.1) No T assessment, n (%) 6 (1.7) 5 (1.4) 2 (0.6) 8 (2.3) 3 (0.8) 1 (0.3) 5 (1.4) 1 (0.3) 1 (0.3) Data cutoff: January 31, 2023. The denominator for all percentages is the number of pts in the safety population. † T assessment at 12, 24, or 36 months ± 6-week window of recovery to >175 ng/dL. ‡ T assessment at 12, 24, or 36 months ± 6-week window of recovery to >250 ng/dL. § T assessment at 12, 24, or 36 months ± 6-week window of recovery to ≥baseline T.