Abstract 2740
Background
ICELAND is a large multicentre EU study demonstrating similar efficacy, tolerability and QOL with CAD and intermittent androgen deprivation (IAD) with leuprorelin (Eligard®) in non-metastatic PC. This post hoc analysis investigated if patients (pts) achieving serum testosterone (T) levels of ≤20 ng/dL within the 1st year of CAD have improved cause-specific survival (CSS) and time to PSA [castrate-resistant prostate cancer (CRPC)] progression.
Methods
Pts with locally advanced or relapsing non-metastatic PC following radical prostatectomy or radiotherapy were enrolled in this prospective, phase IIIb, open-label, randomised study (NCT00378690). After a 6-month induction with leuprorelin (Eligard®) 3-month depot 22.5 mg (plus bicalutamide 50 mg/day for 1 month), pts with PSA levels ≤1 ng/mL were randomised 1:1 to CAD (n = 361) or IAD (n = 340) with leuprorelin (Eligard®) for 36 months. Pts receiving CAD therapy were stratified by min, median and max T levels achieved during the 1st year of therapy into ≤20, 20-50 and >50 ng/dL T subgroups. CSS and time to PSA (CRPC) progression were analysed by Kaplan-Meier analyses and Cox proportional hazards regression model.
Results
A total of 90.1%, 83.5% and 74.5% of pts receiving CAD achieved minimum, median and maximum serum T levels of ≤20 ng/dL, respectively. CSS rates and time to PSA (CRPC) progression did not differ significantly between T subgroups (table).
| Testosterone level (ng/dL) | N | Time to cause-specific survival | Time to PSA (CRPC) progression | ||||
|---|---|---|---|---|---|---|---|
| % (95% CI) | HR (95% CI) | p valuea | % (95% CI) | HR (95% CI) | p valuea | ||
| Minimum | |||||||
| ≤20 | 311 | 90.5 (87.2–93.8) | 1 | 99.0 (97.9–100.0) | 1 | ||
| >20 − ≤50 | 33 | 86.7 (74.5–100.0) | 0.89 (0.4–1.8) | 0.849 | 92.4 (83.3–100.0) | 5.06 (1.3–16.1) | 0.062 |
| >50 | 1 | 100.0 (100.0–100.0) | NE | 100.0 (100.0–100.0) | NE | ||
| Median | |||||||
| ≤20 | 288 | 90.2 (86.8–93.7) | 1 | 98.9 (97.8–100.0) | 1 | ||
| >20 − ≤50 | 54 | 89.1 (80.6–98.9) | 0.84 (0.4–1.6) | 0.598 | 95.4 (89.8–100.0) | 3.92 (1.2–12.3) | 0.083 |
| >50 | 3 | 83.3 (56.7–100.0) | 2.74 (0.2–12.7) | 100.0 (100.0–100.0) | NE | ||
| Maximum | |||||||
| ≤20 | 257 | 90.6 (87.0–94.2) | 1 | 99.2 (98.1–100.0) | 1 | ||
| >20 − ≤50 | 78 | 87.8 (80.3–95.5) | 1.13 (0.6–1.9) | 0.196 | 96.8 (92.9–100.0) | 2.79 (0.8–9.3) | 0.165 |
| >50 | 10 | 83.3 (59.5–100.0) | 3.59 (0.9–10.0) | 95.0 (85.7–100.0) | 4.57 (0.2–26.8) | ||
CI, confidence interval; HR, hazard ratio; CRPC, castrate-resistant prostate cancer; NE, not estimable; PSA, prostate-specific antigen. aLikelihood ratio test.
Conclusions
In pts receiving CAD, CSS and time to PSA (CRPC) progression did not differ according to T levels in the 1st year of therapy. This finding may have been due, at least in part, to the effectiveness of leuprorelin (Eligard®) in lowering T, as maximum T levels ≤20 ng/dL were achieved in 75% of pts over the 1st year of CAD.
Legal entity responsible for the study
Astellas Pharma, Inc. and Medivation, Inc.
Funding
Astellas Pharma, Inc. and Medivation, Inc.
Disclosure
B. Tombal: Advisory board member: Astellas, Bayer, Medivation, Ferring, Amgen, Sanofi. Aventis. Corporate-sponsored research: Astellas, Bayer, Medivation, Ferring, Amgen, Sanofi Aventis.
T.L. Tammela: Advisory board member: Astellas, Orion Pharma, Bayer. Corporate-sponsored research: Astellas, Orion Pharma, Medivation, Jansen-Cilag, Bayer, Ferring, Camurus Ab, Lidds Ab.
All other authors have declared no conflicts of interest.