Per-Anders Abrahamsson1, Laurent Boccon-Gibod2, Juan Morote3, Igle Jan de Jong4, Anders Malmberg5, Anders Neijber6, Peter Albers7. 1. Department of Urology, Skåne University Hospital, Lund University, Malmö, Sweden. Electronic address: per-anders.abrahamsson@ferring.com. 2. Membre de l'Académie de Chirurgie, Expert près les Tribunaux, Paris, France. 3. Department of Urology, Vall d'Hebron Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain. 4. Department of Urology, University Medical Center Groningen, University of Groningen, The Netherlands. 5. Clinical R&D, Global Biometrics, Ferring Pharmaceuticals, Copenhagen, Denmark. 6. Clinical R&D, Urology, Ferring Pharmaceuticals, Copenhagen, Denmark. 7. Department of Urology, Düsseldorf University Hospital, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Abstract
BACKGROUND: Intermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). OBJECTIVE: To evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. DESIGN, SETTING, AND PARTICIPANTS: This multivariable analysis included 191 prostate cancer patients with baseline PSA 4-50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. RESULTS: The full five-factor model showed that baseline PSA (p<0.0001), age (p=0.004), prostate cancer stage/previous therapy (p=0.023), and baseline testosterone (p=0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p<0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p<0.0001) and age (p=0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. CONCLUSION: Patients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelix IAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. PATIENT SUMMARY: We describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00801242.
BACKGROUND: Intermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). OBJECTIVE: To evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. DESIGN, SETTING, AND PARTICIPANTS: This multivariable analysis included 191 prostate cancerpatients with baseline PSA 4-50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. RESULTS: The full five-factor model showed that baseline PSA (p<0.0001), age (p=0.004), prostate cancer stage/previous therapy (p=0.023), and baseline testosterone (p=0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p<0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p<0.0001) and age (p=0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. CONCLUSION:Patients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelixIAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. PATIENT SUMMARY: We describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00801242.