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MP73-20 INTERMITTENT VERSUS CONTINUOUS ANDROGEN DEPRIVATION IN PATIENTS WITH RELAPSING OR LOCALLY ADVANCED PROSTATE CANCER: A PHASE 3B RANDOMIZED STUDY (ICELAND)
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THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Monday, May 18, 2015
Table 1 Adjusted risk of all cause mortality for men undergoing primary androgen deprivation therapy, relative to observation for localized and locally advanced prostate cancer, stratified by life expectancy and disease ^V“Medicare 1992-2009 severity. SEERa Standard Cox model Co-Morbidity Adjusted life expectancy Under 5 years HR (95% CI)
pvalue
5-10 years HR (95% CI)
pvalue
Over 10 years HR (95% CI)
pvalue
T1/T2 Low Risk*
0.95 (0.831.09)
0.5
1.11 (1.061.17)
<0.001
1.39 (1.321.46)
<0.001
T1/T2 High Risk*
0.91 (0.791.04)
0.16
1.17 (1.101.25)
<0.001
1.51 (1.411.63)
<0.001
T3
0.54 (0.30.98)
0.04
1.26 (1.061.51)
0.01
1.98 (1.742.27)
<0.001
Propensity weighted Cox proportional hazards model+ Co-Morbidity Adjusted life expectancy Under 5 years HR (95% CI)
pvalue
5-10 years HR (95% CI)
pvalue
Over 10 years HR (95% CI)
pvalue
T1/T2 Low Risk*
0.96 (0.841.1)
0.6
1.1 (1.051.16)
<0.001
1.36 (1.281.44)
<0.001
T1/T2 High Risk*
0.85 (0.750.98)
0.02
1.11 (1.041.18)
0.001
1.46 (1.351.57)
<0.001
T3
0.79 (0.491.29)
0.3
1.27 (0.941.35)
0.2
1.78 (1.562.04)
<0.001
Abbreviations: HR, hazard ration; CI, confidence interval; pADT, primary androgen deprivation therapy +-Covariates included age at diagnosis, year at diagnosis, race, marital status, population density, census tract income and educational attainment, Charleson Comorbidity Index & pADT percent in ^VÔs HSA. *- Prior to 2003 Gleason grade of 2-4, 5-7, and 8-10 correpatienta sponded to well-differentiated (AJCC grade 1), moderately (AJCC grade 2) differentiated, and poorly differentiated disease (AJCC grade 3), respectively. Thereafter a Gleason grade of 2-4, 5-6, and 7-10 corresponded to well-differentiated, moderately differentiated, and poorly differentiated CaP. Well and moderately differentiated cancers constitute the low risk group.
MP73-20 INTERMITTENT VERSUS CONTINUOUS ANDROGEN DEPRIVATION IN PATIENTS WITH RELAPSING OR LOCALLY ADVANCED PROSTATE CANCER: A PHASE 3B RANDOMIZED STUDY (ICELAND) Claude Schulman, Brussels, Belgium; Erik Cornel, Hengelo, Netherlands; Vsevolod Matveev, Moscow, Russian Federation; Jan Schraml, Usti nad Laben, Czech Republic; Henri Bensadoun, Lormont, France; Wolfgang Warnack, Hagenow, Germany; Raj Persad, Bristol, United Kingdom; Marek Salagierski, Lodz, Poland; Francisco Gomez Viega, A Coruna, Spain; Edwina Baskin-Bey, Beatriz Lopez, Leiden, Netherlands; Bertrand Tombal*, Brussels, Belgium INTRODUCTION AND OBJECTIVES: Studies of intermittent androgen deprivation (IAD) vs continuous androgen deprivation (CAD) in prostate cancer (PCa) have provided conflicting results due to heterogeneous design, patient (pt) populations and treatment schedules. The objective of ICELAND, a large multicenter European (EU) study in pts with relapsing M0 or locally advanced (LCA) PCa, with follow-up across multiple objective outcome measures, was to increase knowledge regarding the efficacy and safety profile of IAD vs. CAD. METHODS: 933 pts with LCA or relapsing M0 PCa following radical prostatectomy or radiotherapy, Gleason score 6, and life expectancy 5 years were enrolled in this prospective, phase 3b, open-label, randomized study. After a 6-month (m) induction with leuprorelin 3-m depot 22.5 mg (plus bicalutamide 50 mg/day for 1 m), 701 pts with prostate-specific antigen (PSA) levels 1 ng/mL were randomized 1:1 to either CAD or IAD with leuprorelin for 36 m. The primary endpoint was time to PSA progression (TTPP; 3 consecutive increasing PSA values 4 ng/mL 2 weeks apart). Pts were subsequently followed at 6-m intervals for 18 m to assess overall survival (OS). Secondary endpoints included OS, time to serum testosterone >50 ng/dL, and quality of life (QoL) measured by EORTC QLQ-30. RESULTS: Of the 701 randomized pts, 58% had LCA PCa and 42% had relapsing M0 PCa. The CAD and IAD groups were comparable at baseline. Median (range) number of injections administered during the randomized phase was 12.0 (1-12) and 3.0 (1-10), respectively. TTPP did not differ significantly between the two groups; estimated 3-year PSA progression rates were 10.6% and 10.1%, respectively (p¼0.718). There were no statistically significant differences between groups for PSA progression-free survival (p¼0.865), mean PSA levels over time, QoL, or OS; estimated 5-year OS was 85.0% for CAD and 81.8% for IAD (p¼0.969). 330 pts (93.8%) in the CAD group maintained testosterone levels <50ng/dL throughout treatment. Most adverse events (AEs) were mild or moderate; the most common AEs were hot flush (CAD: 19%, IAD: 21%) and hypertension (CAD: 13%, IAD: 11%). Analysis of AEs in pts with LCA vs. relapsing M0 PCa at baseline revealed no differences between CAD and IAD regarding number of AEs, serious AEs, or AEs leading to drug discontinuation. CONCLUSIONS: IAD and CAD demonstrated similar efficacy, tolerability, and QoL. IAD may be a valid option for select pts with LCA or relapsing M0 PCa. Source of Funding: Astellas Pharma, Inc
Source of Funding: None
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Monday, May 18, 2015
Table 1 Adjusted risk of all cause mortality for men undergoing primary androgen deprivation therapy, relative to observation for localized and locally advanced prostate cancer, stratified by life expectancy and disease ^V“Medicare 1992-2009 severity. SEERa Standard Cox model Co-Morbidity Adjusted life expectancy Under 5 years HR (95% CI)
pvalue
5-10 years HR (95% CI)
pvalue
Over 10 years HR (95% CI)
pvalue
T1/T2 Low Risk*
0.95 (0.831.09)
0.5
1.11 (1.061.17)
<0.001
1.39 (1.321.46)
<0.001
T1/T2 High Risk*
0.91 (0.791.04)
0.16
1.17 (1.101.25)
<0.001
1.51 (1.411.63)
<0.001
T3
0.54 (0.30.98)
0.04
1.26 (1.061.51)
0.01
1.98 (1.742.27)
<0.001
Propensity weighted Cox proportional hazards model+ Co-Morbidity Adjusted life expectancy Under 5 years HR (95% CI)
pvalue
5-10 years HR (95% CI)
pvalue
Over 10 years HR (95% CI)
pvalue
T1/T2 Low Risk*
0.96 (0.841.1)
0.6
1.1 (1.051.16)
<0.001
1.36 (1.281.44)
<0.001
T1/T2 High Risk*
0.85 (0.750.98)
0.02
1.11 (1.041.18)
0.001
1.46 (1.351.57)
<0.001
T3
0.79 (0.491.29)
0.3
1.27 (0.941.35)
0.2
1.78 (1.562.04)
<0.001
Abbreviations: HR, hazard ration; CI, confidence interval; pADT, primary androgen deprivation therapy +-Covariates included age at diagnosis, year at diagnosis, race, marital status, population density, census tract income and educational attainment, Charleson Comorbidity Index & pADT percent in ^VÔs HSA. *- Prior to 2003 Gleason grade of 2-4, 5-7, and 8-10 correpatienta sponded to well-differentiated (AJCC grade 1), moderately (AJCC grade 2) differentiated, and poorly differentiated disease (AJCC grade 3), respectively. Thereafter a Gleason grade of 2-4, 5-6, and 7-10 corresponded to well-differentiated, moderately differentiated, and poorly differentiated CaP. Well and moderately differentiated cancers constitute the low risk group.
MP73-20 INTERMITTENT VERSUS CONTINUOUS ANDROGEN DEPRIVATION IN PATIENTS WITH RELAPSING OR LOCALLY ADVANCED PROSTATE CANCER: A PHASE 3B RANDOMIZED STUDY (ICELAND) Claude Schulman, Brussels, Belgium; Erik Cornel, Hengelo, Netherlands; Vsevolod Matveev, Moscow, Russian Federation; Jan Schraml, Usti nad Laben, Czech Republic; Henri Bensadoun, Lormont, France; Wolfgang Warnack, Hagenow, Germany; Raj Persad, Bristol, United Kingdom; Marek Salagierski, Lodz, Poland; Francisco Gomez Viega, A Coruna, Spain; Edwina Baskin-Bey, Beatriz Lopez, Leiden, Netherlands; Bertrand Tombal*, Brussels, Belgium INTRODUCTION AND OBJECTIVES: Studies of intermittent androgen deprivation (IAD) vs continuous androgen deprivation (CAD) in prostate cancer (PCa) have provided conflicting results due to heterogeneous design, patient (pt) populations and treatment schedules. The objective of ICELAND, a large multicenter European (EU) study in pts with relapsing M0 or locally advanced (LCA) PCa, with follow-up across multiple objective outcome measures, was to increase knowledge regarding the efficacy and safety profile of IAD vs. CAD. METHODS: 933 pts with LCA or relapsing M0 PCa following radical prostatectomy or radiotherapy, Gleason score 6, and life expectancy 5 years were enrolled in this prospective, phase 3b, open-label, randomized study. After a 6-month (m) induction with leuprorelin 3-m depot 22.5 mg (plus bicalutamide 50 mg/day for 1 m), 701 pts with prostate-specific antigen (PSA) levels 1 ng/mL were randomized 1:1 to either CAD or IAD with leuprorelin for 36 m. The primary endpoint was time to PSA progression (TTPP; 3 consecutive increasing PSA values 4 ng/mL 2 weeks apart). Pts were subsequently followed at 6-m intervals for 18 m to assess overall survival (OS). Secondary endpoints included OS, time to serum testosterone >50 ng/dL, and quality of life (QoL) measured by EORTC QLQ-30. RESULTS: Of the 701 randomized pts, 58% had LCA PCa and 42% had relapsing M0 PCa. The CAD and IAD groups were comparable at baseline. Median (range) number of injections administered during the randomized phase was 12.0 (1-12) and 3.0 (1-10), respectively. TTPP did not differ significantly between the two groups; estimated 3-year PSA progression rates were 10.6% and 10.1%, respectively (p¼0.718). There were no statistically significant differences between groups for PSA progression-free survival (p¼0.865), mean PSA levels over time, QoL, or OS; estimated 5-year OS was 85.0% for CAD and 81.8% for IAD (p¼0.969). 330 pts (93.8%) in the CAD group maintained testosterone levels <50ng/dL throughout treatment. Most adverse events (AEs) were mild or moderate; the most common AEs were hot flush (CAD: 19%, IAD: 21%) and hypertension (CAD: 13%, IAD: 11%). Analysis of AEs in pts with LCA vs. relapsing M0 PCa at baseline revealed no differences between CAD and IAD regarding number of AEs, serious AEs, or AEs leading to drug discontinuation. CONCLUSIONS: IAD and CAD demonstrated similar efficacy, tolerability, and QoL. IAD may be a valid option for select pts with LCA or relapsing M0 PCa. Source of Funding: Astellas Pharma, Inc
Source of Funding: None