Prostate Cancer
Conditions
Brief summary
The purpose of this study is to assess the benefit of immediate hormonal treatment after Radical Prostatectomy in Chinese and Russian patients with high risk prostate cancer. To reach this target, the trial will compare a group of patients treated with triptorelin at 8 weeks after the surgery and for a duration of 9 months (3 injections) versus another group (called active surveillance group) who will be not receiving triptorelin. Both groups will be followed every 3 months to monitor any sign of disease progression during a minimum of 36 months
Detailed description
This trial is a phase IV (in Russia and China) as approved indication is locally advanced or metastatic prostate cancer in both countries.
Interventions
Triptorelin, one injection every 3 months. A total of 3 injections (at baseline, 3 and 6 months)
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathologically confirmed adenocarcinoma of the prostate * Radical Prostatectomy with curative intent performed no more than 8 weeks before randomisation * High risk criteria of disease progression, defined as follows: Gleason score ≥8 on prostatectomy specimen, and/or Pre RP PSA level ≥20 ng/mL, and/or Primary tumour stage 3a (pT3a) (with any PSA level and any Gleason score) * Post-RP PSA levels ≤0.2 ng/mL at 6 weeks
Exclusion criteria
* Evidence of lymph nodes or distant metastasis * Positive margins * Evidence of any other malignant disease, not treated with a curative intent * Had surgical castration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With BR Events | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | The primary efficacy analyses of Biochemical Relapse-Free Survival (BRFS) was performed after 61 BR events were observed on the study global level. The number of subjects with BR events per treatment group is reported. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. |
| Median Time to BRFS | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or first quartile (Q1) (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports median time to BRFS (with Q1 time to BRFS reported in the subsequent outcome measure). |
| Q1 Time to BRFS | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports Q1 time to BRFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Q1 Time to OS | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports Q1 time to OS. |
| Time to Disease-specific Mortality | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | Disease-specific mortality was measured as the time between randomisation and death related to prostate cancer. |
| Median Time to PSA Doubling Time (PSADT) | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports median time to PSADT (with Q1 time to PSADT reported in the subsequent outcome measure). |
| Q1 Time to PSADT | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports Q1 time to PSADT. |
| Median Time to Event-Free Survival (EFS) | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports median time to EFS (with Q1 time to EFS reported in the subsequent outcome measure). |
| Change From Baseline in Serum Testosterone Levels | Baseline (Day 1) and Months 3, 6 and 9. | Serum testosterone levels were evaluated on blood samples taken before triptorelin injection at baseline and at 3, 6 and 9 months only in subjects in the triptorelin arm. Change from baseline in testosterone levels are reported as median values at Months 3, 6 and 9. Note: the raw baseline values for testosterone levels are reported in the Baseline Characteristics section. |
| Change From Baseline in FACT-P Total Score | Baseline (Day 1) and Months 9, 24 and 36. | Health-Related Quality of Life (HRQoL) was assessed using the FACT-P questionnaire (v4) at baseline and at 9, 24 and 36 months. The FACT-P score is composed of 27 general questions about physical, social, emotional, and functional well-being, as well as a 12-item questionnaire about prostate-specific concerns. The total FACT-P score was calculated as the sum of 39 item scores (range of 0-156); higher scores indicate a better quality of life. Change from baseline in FACT-P total score are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for FACT-P total score are reported in the Baseline Characteristics section. |
| Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | Baseline (Day 1) and Months 9, 24 and 36. | HRQoL was assessed using the SF-36 health survey (v2) at baseline and at 9, 24 and 36 months. The 36 items cover 8 health domains: PF, role-physical, BP, SF, MH, RE, VT and GH. Subscale scores were normed to the 2009 US general population (mean=50; SD=10) to give norm-based scores. Two summary measures were then calculated: PCS was derived from PF, role-physical, BP and GH; MCS was derived from SF, MH, RE and VT. The PCS and MCS norm-based scores ranged 0-100; higher scores indicate a better QoL. Change from baseline in SF-36 PCS and MSC norm-based scores are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for PCS and MSC norm-based scores are reported in the Baseline Characteristics section. |
| Percent Change From Baseline in PSA Levels | Screening (Day -14) and Months 3, 6, 9, 12, 24 and 36. | As per inclusion criterion, all subjects in both treatment groups had PSA levels ≤0.2 ng/mL at the screening visit. Starting from Month 3, any elevated PSA concentration \>0.2 ng/mL had to be confirmed by a second measurement performed 4 to 6 weeks later. No confirmation test was required after evidence of disease progression (BR and/or clinical disease progression). Subjects remained in the study until Month 36, even if they had a biochemical failure (PSA levels \>0.2 ng/mL); then they could enter follow-up. The percent change from baseline was defined as the percent change from the screening visit (Day -14). Percent change from baseline in PSA levels are reported as median values at Months 3, 6, 9, 12, 24 and 36. Note: the raw baseline values for PSA levels are reported in the Baseline Characteristics section. |
| Q1 Time to EFS | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports Q1 time to EFS. |
| Median Time to Overall Survival (OS) | Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). | OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports median time to OS (with Q1 time to OS reported in the subsequent outcome measure). |
Countries
China, Russia
Participant flow
Recruitment details
The study was conducted in male subjects with high-risk prostate cancer who had undergone radical prostatectomy (RP) in 18 sites in China and Russia between Dec 2012 and Sep 2019. The study participation for each subject was at least 36 months. The end of study was when 61 biochemical relapse (BR) events were observed on the study global level.
Pre-assignment details
Subjects had to have undergone RP no more than 8 weeks prior to randomisation, with post-RP prostate specific antigen (PSA) levels ≤0.2 nanograms/millilitre (ng/mL). The screening visit took place 6 weeks after RP (i.e. 2 weeks prior to randomisation). No other treatment for prostate cancer was permitted.
Participants by arm
| Arm | Count |
|---|---|
| Active Surveillance Subjects were treated according to each study centre's standard of care. No adjuvant treatment with any method (hormonal treatment and/or surgical castration and/or radiation therapy) was initiated prior to evidence of disease progression (clinical or biochemical). | 117 |
| Triptorelin Subjects were treated with triptorelin as a hormonal adjuvant to RP and received intramuscular injections of 11.25 mg triptorelin every 3 months for a total of 3 injections (at baseline, 3 months and 6 months). | 109 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event (up to Month 36) | 1 | 1 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Did not attend end of study visit | 7 | 8 |
| Overall Study | Lost to Follow-up | 7 | 2 |
| Overall Study | Withdrawal by Subject | 26 | 23 |
Baseline characteristics
| Characteristic | Active Surveillance | Triptorelin | Total |
|---|---|---|---|
| 36-Item Short Form Health Survey (SF-36) Score Mental Component Summary (MCS) | 48.18 scores on a scale STANDARD_DEVIATION 9.78 | 47.41 scores on a scale STANDARD_DEVIATION 9.59 | 47.81 scores on a scale STANDARD_DEVIATION 9.67 |
| 36-Item Short Form Health Survey (SF-36) Score Physical Component Summary (PCS) | 46.31 scores on a scale STANDARD_DEVIATION 6.49 | 47.37 scores on a scale STANDARD_DEVIATION 6.62 | 46.81 scores on a scale STANDARD_DEVIATION 6.56 |
| Age, Continuous | 65.3 years STANDARD_DEVIATION 6.8 | 65.4 years STANDARD_DEVIATION 6.1 | 65.3 years STANDARD_DEVIATION 6.4 |
| Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score | 113.26 scores on a scale STANDARD_DEVIATION 18.64 | 114.98 scores on a scale STANDARD_DEVIATION 18.31 | 114.08 scores on a scale STANDARD_DEVIATION 18.46 |
| Gleason Score Prior to RP - Total Score in Categories ≤ 6 | 31 Participants | 27 Participants | 58 Participants |
| Gleason Score Prior to RP - Total Score in Categories = 7 (3+4) | 32 Participants | 27 Participants | 59 Participants |
| Gleason Score Prior to RP - Total Score in Categories = 7 (4+3) | 19 Participants | 20 Participants | 39 Participants |
| Gleason Score Prior to RP - Total Score in Categories ≥ 8 | 29 Participants | 31 Participants | 60 Participants |
| PSA Levels | 0.074 ng/mL | 0.074 ng/mL | 0.074 ng/mL |
| Race/Ethnicity, Customized Asian | 84 Participants | 79 Participants | 163 Participants |
| Race/Ethnicity, Customized Caucasian / White | 33 Participants | 30 Participants | 63 Participants |
| Region of Enrollment China | 84 Participants | 79 Participants | 163 Participants |
| Region of Enrollment Russia | 33 Participants | 30 Participants | 63 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 117 Participants | 109 Participants | 226 Participants |
| Testosterone Levels | — | 462.00 nanograms per deciliter (ng/dL) | 462.00 nanograms per deciliter (ng/dL) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 112 | 0 / 105 | 2 / 217 |
| other Total, other adverse events | 27 / 112 | 31 / 105 | 7 / 217 |
| serious Total, serious adverse events | 11 / 112 | 3 / 105 | 2 / 217 |
Outcome results
Primary
Median Time to BRFS
BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or first quartile (Q1) (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports median time to BRFS (with Q1 time to BRFS reported in the subsequent outcome measure).
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Surveillance | Median Time to BRFS | NA months |
| Triptorelin | Median Time to BRFS | NA months |
Comparison: A two-sided log-rank test was used to compare time to BRFS between both treatment groups.p-value: 0.158Log Rank
Comparison: Comparison between treatment groups: Triptorelin compared to Active surveillance.~A Cox proportional hazard model was fitted to compute hazards ratios (HRs) and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.195% CI: [0.38, 1.09]Regression, Cox
Comparison: Comparison between countries: Russia compared to China.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.50295% CI: [0.46, 4.79]Regression, Cox
Comparison: Centre effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.671Regression, Cox
Comparison: Comparison between Gleason score categories: Gleason score of =7 compared to Gleason score ≤6.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.09395% CI: [0.87, 6.39]Regression, Cox
Comparison: Comparison between Gleason score categories: Gleason score of ≥8 compared to Gleason score ≤6.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.16895% CI: [0.74, 5.55]Regression, Cox
Primary
Number of Subjects With BR Events
The primary efficacy analyses of Biochemical Relapse-Free Survival (BRFS) was performed after 61 BR events were observed on the study global level. The number of subjects with BR events per treatment group is reported. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Surveillance | Number of Subjects With BR Events | 35 Participants |
| Triptorelin | Number of Subjects With BR Events | 26 Participants |
Primary
Q1 Time to BRFS
BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports Q1 time to BRFS.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Surveillance | Q1 Time to BRFS | 30.0 months |
| Triptorelin | Q1 Time to BRFS | 39.1 months |
Secondary
Change From Baseline in FACT-P Total Score
Health-Related Quality of Life (HRQoL) was assessed using the FACT-P questionnaire (v4) at baseline and at 9, 24 and 36 months. The FACT-P score is composed of 27 general questions about physical, social, emotional, and functional well-being, as well as a 12-item questionnaire about prostate-specific concerns. The total FACT-P score was calculated as the sum of 39 item scores (range of 0-156); higher scores indicate a better quality of life. Change from baseline in FACT-P total score are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for FACT-P total score are reported in the Baseline Characteristics section.
Time frame: Baseline (Day 1) and Months 9, 24 and 36.
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects with data available were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active Surveillance | Change From Baseline in FACT-P Total Score | Month 36 | 2.76 score on a scale |
| Active Surveillance | Change From Baseline in FACT-P Total Score | Month 9 | 4.75 score on a scale |
| Active Surveillance | Change From Baseline in FACT-P Total Score | Month 24 | 1.48 score on a scale |
| Triptorelin | Change From Baseline in FACT-P Total Score | Month 24 | 3.78 score on a scale |
| Triptorelin | Change From Baseline in FACT-P Total Score | Month 36 | 3.81 score on a scale |
| Triptorelin | Change From Baseline in FACT-P Total Score | Month 9 | 0.88 score on a scale |
Secondary
Change From Baseline in Serum Testosterone Levels
Serum testosterone levels were evaluated on blood samples taken before triptorelin injection at baseline and at 3, 6 and 9 months only in subjects in the triptorelin arm. Change from baseline in testosterone levels are reported as median values at Months 3, 6 and 9. Note: the raw baseline values for testosterone levels are reported in the Baseline Characteristics section.
Time frame: Baseline (Day 1) and Months 3, 6 and 9.
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects in the triptorelin arm with data available were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Surveillance | Change From Baseline in Serum Testosterone Levels | Month 9 | -429.80 ng/dL |
| Active Surveillance | Change From Baseline in Serum Testosterone Levels | Month 3 | -444.60 ng/dL |
| Active Surveillance | Change From Baseline in Serum Testosterone Levels | Month 6 | -438.80 ng/dL |
Secondary
Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS)
HRQoL was assessed using the SF-36 health survey (v2) at baseline and at 9, 24 and 36 months. The 36 items cover 8 health domains: PF, role-physical, BP, SF, MH, RE, VT and GH. Subscale scores were normed to the 2009 US general population (mean=50; SD=10) to give norm-based scores. Two summary measures were then calculated: PCS was derived from PF, role-physical, BP and GH; MCS was derived from SF, MH, RE and VT. The PCS and MCS norm-based scores ranged 0-100; higher scores indicate a better QoL. Change from baseline in SF-36 PCS and MSC norm-based scores are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for PCS and MSC norm-based scores are reported in the Baseline Characteristics section.
Time frame: Baseline (Day 1) and Months 9, 24 and 36.
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects with data available were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 36 | 4.79 score on a scale |
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 24 | 4.49 score on a scale |
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 9 | 1.80 score on a scale |
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 24 | 0.55 score on a scale |
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 36 | 1.13 score on a scale |
| Active Surveillance | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 9 | 2.78 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 36 | 5.10 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 9 | 2.60 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 24 | 3.46 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | PCS: Month 36 | 4.86 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 9 | 4.26 score on a scale |
| Triptorelin | Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | MCS: Month 24 | 2.81 score on a scale |
Secondary
Median Time to Event-Free Survival (EFS)
EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports median time to EFS (with Q1 time to EFS reported in the subsequent outcome measure).
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Surveillance | Median Time to Event-Free Survival (EFS) | NA months |
| Triptorelin | Median Time to Event-Free Survival (EFS) | NA months |
Comparison: A two-sided log-rank test was used to compare time to EFS between both treatment groups.p-value: 0.639Log Rank
Comparison: Comparison between treatment groups: Triptorelin compared to Active surveillance.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.65395% CI: [0.24, 9.59]Regression, Cox
Comparison: Country effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.999Regression, Cox
Comparison: Centre effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 1Regression, Cox
Comparison: Gleason score effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.583Regression, Cox
Secondary
Median Time to Overall Survival (OS)
OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports median time to OS (with Q1 time to OS reported in the subsequent outcome measure).
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Surveillance | Median Time to Overall Survival (OS) | NA months |
| Triptorelin | Median Time to Overall Survival (OS) | NA months |
Comparison: A two-sided log-rank test was used to compare time to OS between both treatment groups.p-value: 0.557Log Rank
Secondary
Median Time to PSA Doubling Time (PSADT)
PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports median time to PSADT (with Q1 time to PSADT reported in the subsequent outcome measure).
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects with increased PSA \>0.2 ng/mL and with data available were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Surveillance | Median Time to PSA Doubling Time (PSADT) | NA months |
| Triptorelin | Median Time to PSA Doubling Time (PSADT) | NA months |
Comparison: A two-sided log-rank test was used to compare PSADT between both treatment groups.p-value: 0.525Log Rank
Comparison: Comparison between treatment groups: Triptorelin compared to Active surveillance.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.43595% CI: [0.44, 6.73]Regression, Cox
Comparison: Country effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.761Regression, Cox
Comparison: Centre effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.652Regression, Cox
Comparison: Gleason score effect.~A Cox proportional hazard model was fitted to compute HRs and the corresponding 95% CIs with treatment group, country (China as reference), centre (the largest centre as reference), and Gleason score on prostatectomy specimen (in categories: ≤6 / =7 / ≥8, with ≤6 considered as the reference) as fixed factors.p-value: 0.726Regression, Cox
Secondary
Percent Change From Baseline in PSA Levels
As per inclusion criterion, all subjects in both treatment groups had PSA levels ≤0.2 ng/mL at the screening visit. Starting from Month 3, any elevated PSA concentration \>0.2 ng/mL had to be confirmed by a second measurement performed 4 to 6 weeks later. No confirmation test was required after evidence of disease progression (BR and/or clinical disease progression). Subjects remained in the study until Month 36, even if they had a biochemical failure (PSA levels \>0.2 ng/mL); then they could enter follow-up. The percent change from baseline was defined as the percent change from the screening visit (Day -14). Percent change from baseline in PSA levels are reported as median values at Months 3, 6, 9, 12, 24 and 36. Note: the raw baseline values for PSA levels are reported in the Baseline Characteristics section.
Time frame: Screening (Day -14) and Months 3, 6, 9, 12, 24 and 36.
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects with data available were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 6 | 0.0 percent change |
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 12 | 0.0 percent change |
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 24 | 0.0 percent change |
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 3 | 0.0 percent change |
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 36 | 0.0 percent change |
| Active Surveillance | Percent Change From Baseline in PSA Levels | Month 9 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 36 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 6 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 9 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 12 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 24 | 0.0 percent change |
| Triptorelin | Percent Change From Baseline in PSA Levels | Month 3 | 0.0 percent change |
Secondary
Q1 Time to EFS
EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports Q1 time to EFS.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Surveillance | Q1 Time to EFS | NA months |
| Triptorelin | Q1 Time to EFS | NA months |
Secondary
Q1 Time to OS
OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports Q1 time to OS.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Surveillance | Q1 Time to OS | NA months |
| Triptorelin | Q1 Time to OS | NA months |
Secondary
Q1 Time to PSADT
PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports Q1 time to PSADT.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: The ITT population consisted of all randomised subjects analysed according to the group to which they were randomised (i.e. regardless of treatment approach followed). Only subjects with increased PSA \>0.2 ng/mL and with data available were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Surveillance | Q1 Time to PSADT | 13.4 months |
| Triptorelin | Q1 Time to PSADT | 9.1 months |
Secondary
Time to Disease-specific Mortality
Disease-specific mortality was measured as the time between randomisation and death related to prostate cancer.
Time frame: Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored).
Population: Analysis was not performed for this outcome measure as no deaths due to prostate cancer were observed during the study.