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Editor’s comment Enzalutamide, as a new generation of androgen receptor inhibitor, has been approved by the National Medical Products Administration (NMPA) of China for non-metastatic castration-resistant prostate cancer (nmCRPC) patients with a high risk of metastasis.
The approval of an indication is based on the results of the PROSPER study.
February 11-13, 2021, on the occasion of the Spring Festival, the American Society of Clinical Oncology Symposium on Urogenital System Oncology (ASCO-GU) will be held in the form of cloud.
The world's leading experts in the field of urinary oncology gather online to participate in the grand event .
In this meeting, there was a report on the PROSPER study based on the post-mortem analysis of different dimensions such as age, region, and PSA reduction degree.
The editor specially summarized the following for readers.
01Abstract 84Prosper study based on age and region post-mortem analysis: enzalutamide + ADT for the OS and safety of nmCRPC patients 1 previous reports on PROSPER studies showed that enzalutamide + androgen deprivation therapy (ADT) Compared with placebo+ADT, it can significantly improve the metastasis-free survival (MFS) and overall survival (OS) of patients with nmCRPC with rapid PSA elevation.
This study is a post-mortem analysis of a PROSPER study based on factors such as age and region.
Study introduction The PROSPER study included 1401 nmCRPC patients (average age 74 years) with PSA doubling time (PSADT) ≤10 months and PSA ≥2ng/ml, and they were randomly assigned to enzalutamide (160mg/day) according to 2:1.
ADT group and placebo+ADT group.
This study performed a multivariate analysis of OS, including age (≤70 years and >70 years), region, and other variables, and further evaluated exposure-adjusted adverse events (AEs) based on age and region.
The results of the study are as follows (Table 1).
The baseline characteristics of the subgroups are relatively balanced.Table 1 Baseline OS of patients in different regions In the total population, enzalutamide significantly improved overall survival compared with placebo (HR 0.
73; 95% CI: 0.
61-0.
89).
The post-hoc analysis of the PROSPER study found that the OS benefit of enzalutamide treatment was similar among populations in various regions (North America, Europe, Asia, and other regions).
Enzalutamide has the same effect in people less than 70 years old and ≥70 years old; compared with placebo, enzalutamide improves OS in the two groups by 28% and 27%, respectively.
Multivariate analysis found two factors affecting OS results, namely the Eastern Cooperative Oncology Group (ECOG) score (1 vs 0; HR 1.
7; 95% CI: 1.
4-2.
1) and Log (PSA) (HR 1.
2; 95%) CI: 1.
1-1.
3), the detailed data are as follows (Table 2).
The results suggest that nmCRPC patients with rapidly rising PSA have an ECOG score of 1 and higher baseline PSA levels are associated with worse OS outcomes.
Table 2 Multivariate Cox analysis results, the safety of OS affecting factors in nmCRPC patients treated with placebo vs enzalutamide.
The post-mortem analysis of the ROSPER study found that the overall safety was consistent among subgroups of different ages and regions, with enzalutamide ≥3 Grade-grade treatment-related adverse events (TEAEs) are more common in people ≥70 years of age.
Research conclusions Enzalutamide can reduce the risk of death in patients with nmCRPC with a rapid increase in PSA, regardless of age or region; the safety of subgroups of different ages and regions is consistent.
Factors affecting OS include an ECOG score of 1 and a higher baseline PSA level.
02Abstract 94PROSPER study is based on post-hoc analysis of the effect of PSA reduction on OS and MFS.
2 ROSPER study final survival analysis (Sternberg et al.
NEJM 2020) showed that enzalutamide significantly improved MFS compared with placebo (36.
6 vs 14.
7 Month; HR 0.
29; 95% CI: 0.
24-0.
35; P＜0.
001) and OS (67.
0 vs 56.
3 months; HR 0.
73; 95% CI: 0.
61-0.
89; P＜0.
001).
The post-hoc analysis of previous ROSPER studies showed that the greater the decrease in PSA, the longer the MFS; compared with patients with no PSA progression, patients with moderate PSA progression have an increased risk of metastasis.
This study further explored the relationship between the degree of PSA reduction and the prognosis of OS and MFS.
Study introduction This PROSPER study included 905 nmCRPC patients treated with enzalutamide in a post-mortem analysis.
PSA assessments were performed at the 17th week and every 16 weeks thereafter.
In this study, patients whose PSA decreased from 0% to <50% were used as the reference group, and the OS and MFS of 4 independent subgroups were evaluated.
The results of the study were the baseline and decline of PSA.
The median baseline PSA level in the enzalutamide group was 11.
1 ng/ml (0.
8-1071) and that in the placebo group was 10.
2 ng/ml (0.
2-468).
86% of the patients in the enzalutamide group had a PSA reduction of ≥50%, and only 3% in the placebo group; the patients in the enzalutamide group had a PSA reduction of ≥90%, up to 65%.
Among patients in the enzalutamide group with a PSA reduction of 50% or more, 90.
3% occurred within the first 17 weeks, and the median time for PSA to drop to its lowest point was 332 days (36-1574).
The OS results of different PSA reduction levels are compared with the maximum PSA reduction degree <50%, and the maximum reduction degree after the application of enzalutamide is 50% to <90%, ≥90%, and the lowest value ≥0.
2ng/ml and ≥90% and The risk of death in patients with the lowest value <0.
2ng/ml was reduced by 51%, 74%, and 90%, respectively. Figure 1 Kaplan-Meier survival analysis of OS in each subgroup of the maximum reduction of PSA.
MFS results of different PSA reductions compared with the group with the maximum reduction of PSA <50%, the maximum reduction after the application of enzalutamide is 50% to <90% The risk of metastasis or death in patients with ≥ 90% and the lowest value ≥ 0.
2 ng/ml and ≥ 90% and the lowest value <0.
2 ng/ml was reduced by 64%, 82%, and 94%, respectively.
Figure 2 Kaplan-Meier survival analysis of MFS in each subgroup of the maximum reduction of PSA.
It can be seen that the maximum reduction of PSA is significantly related to the prognosis of OS and MFS.
Table 3 The relationship between the maximum reduction of PSA and the prognosis of OS and MFS.
Research conclusions For nmCRPC patients who received enzalutamide + ADT and whose PSA increased rapidly, the reduction of PSA was significantly related to the prognosis of OS and MFS.
This study defines PSA through a percentage decrease and an actual decrease of less than 0.
2ng/ml, revealing the relationship between previously neglected PSA indicators, and stressing the importance of the lowest PSA as an intermediate biomarker of nmCRPC. References: Ugo De Giorgi, Maha HA Hussain, Neal D.
Shore, et al.
PROSPER subgroup analysis by age and region: Overall survival and safety in men with nonmetastatic castration-resistant prostate cancer receiving androgen deprivation therapy plus enzalutamide.
2021 ASCO- GU.
Abstract 84.
Maha HA Hussain,Cora N.
Sternberg,Eleni Efstathiou,et al.
Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).
2021 ASCO-GU.
Abstract 94.
The approval of an indication is based on the results of the PROSPER study.
February 11-13, 2021, on the occasion of the Spring Festival, the American Society of Clinical Oncology Symposium on Urogenital System Oncology (ASCO-GU) will be held in the form of cloud.
The world's leading experts in the field of urinary oncology gather online to participate in the grand event .
In this meeting, there was a report on the PROSPER study based on the post-mortem analysis of different dimensions such as age, region, and PSA reduction degree.
The editor specially summarized the following for readers.
01Abstract 84Prosper study based on age and region post-mortem analysis: enzalutamide + ADT for the OS and safety of nmCRPC patients 1 previous reports on PROSPER studies showed that enzalutamide + androgen deprivation therapy (ADT) Compared with placebo+ADT, it can significantly improve the metastasis-free survival (MFS) and overall survival (OS) of patients with nmCRPC with rapid PSA elevation.
This study is a post-mortem analysis of a PROSPER study based on factors such as age and region.
Study introduction The PROSPER study included 1401 nmCRPC patients (average age 74 years) with PSA doubling time (PSADT) ≤10 months and PSA ≥2ng/ml, and they were randomly assigned to enzalutamide (160mg/day) according to 2:1.
ADT group and placebo+ADT group.
This study performed a multivariate analysis of OS, including age (≤70 years and >70 years), region, and other variables, and further evaluated exposure-adjusted adverse events (AEs) based on age and region.
The results of the study are as follows (Table 1).
The baseline characteristics of the subgroups are relatively balanced.Table 1 Baseline OS of patients in different regions In the total population, enzalutamide significantly improved overall survival compared with placebo (HR 0.
73; 95% CI: 0.
61-0.
89).
The post-hoc analysis of the PROSPER study found that the OS benefit of enzalutamide treatment was similar among populations in various regions (North America, Europe, Asia, and other regions).
Enzalutamide has the same effect in people less than 70 years old and ≥70 years old; compared with placebo, enzalutamide improves OS in the two groups by 28% and 27%, respectively.
Multivariate analysis found two factors affecting OS results, namely the Eastern Cooperative Oncology Group (ECOG) score (1 vs 0; HR 1.
7; 95% CI: 1.
4-2.
1) and Log (PSA) (HR 1.
2; 95%) CI: 1.
1-1.
3), the detailed data are as follows (Table 2).
The results suggest that nmCRPC patients with rapidly rising PSA have an ECOG score of 1 and higher baseline PSA levels are associated with worse OS outcomes.
Table 2 Multivariate Cox analysis results, the safety of OS affecting factors in nmCRPC patients treated with placebo vs enzalutamide.
The post-mortem analysis of the ROSPER study found that the overall safety was consistent among subgroups of different ages and regions, with enzalutamide ≥3 Grade-grade treatment-related adverse events (TEAEs) are more common in people ≥70 years of age.
Research conclusions Enzalutamide can reduce the risk of death in patients with nmCRPC with a rapid increase in PSA, regardless of age or region; the safety of subgroups of different ages and regions is consistent.
Factors affecting OS include an ECOG score of 1 and a higher baseline PSA level.
02Abstract 94PROSPER study is based on post-hoc analysis of the effect of PSA reduction on OS and MFS.
2 ROSPER study final survival analysis (Sternberg et al.
NEJM 2020) showed that enzalutamide significantly improved MFS compared with placebo (36.
6 vs 14.
7 Month; HR 0.
29; 95% CI: 0.
24-0.
35; P＜0.
001) and OS (67.
0 vs 56.
3 months; HR 0.
73; 95% CI: 0.
61-0.
89; P＜0.
001).
The post-hoc analysis of previous ROSPER studies showed that the greater the decrease in PSA, the longer the MFS; compared with patients with no PSA progression, patients with moderate PSA progression have an increased risk of metastasis.
This study further explored the relationship between the degree of PSA reduction and the prognosis of OS and MFS.
Study introduction This PROSPER study included 905 nmCRPC patients treated with enzalutamide in a post-mortem analysis.
PSA assessments were performed at the 17th week and every 16 weeks thereafter.
In this study, patients whose PSA decreased from 0% to <50% were used as the reference group, and the OS and MFS of 4 independent subgroups were evaluated.
The results of the study were the baseline and decline of PSA.
The median baseline PSA level in the enzalutamide group was 11.
1 ng/ml (0.
8-1071) and that in the placebo group was 10.
2 ng/ml (0.
2-468).
86% of the patients in the enzalutamide group had a PSA reduction of ≥50%, and only 3% in the placebo group; the patients in the enzalutamide group had a PSA reduction of ≥90%, up to 65%.
Among patients in the enzalutamide group with a PSA reduction of 50% or more, 90.
3% occurred within the first 17 weeks, and the median time for PSA to drop to its lowest point was 332 days (36-1574).
The OS results of different PSA reduction levels are compared with the maximum PSA reduction degree <50%, and the maximum reduction degree after the application of enzalutamide is 50% to <90%, ≥90%, and the lowest value ≥0.
2ng/ml and ≥90% and The risk of death in patients with the lowest value <0.
2ng/ml was reduced by 51%, 74%, and 90%, respectively. Figure 1 Kaplan-Meier survival analysis of OS in each subgroup of the maximum reduction of PSA.
MFS results of different PSA reductions compared with the group with the maximum reduction of PSA <50%, the maximum reduction after the application of enzalutamide is 50% to <90% The risk of metastasis or death in patients with ≥ 90% and the lowest value ≥ 0.
2 ng/ml and ≥ 90% and the lowest value <0.
2 ng/ml was reduced by 64%, 82%, and 94%, respectively.
Figure 2 Kaplan-Meier survival analysis of MFS in each subgroup of the maximum reduction of PSA.
It can be seen that the maximum reduction of PSA is significantly related to the prognosis of OS and MFS.
Table 3 The relationship between the maximum reduction of PSA and the prognosis of OS and MFS.
Research conclusions For nmCRPC patients who received enzalutamide + ADT and whose PSA increased rapidly, the reduction of PSA was significantly related to the prognosis of OS and MFS.
This study defines PSA through a percentage decrease and an actual decrease of less than 0.
2ng/ml, revealing the relationship between previously neglected PSA indicators, and stressing the importance of the lowest PSA as an intermediate biomarker of nmCRPC. References: Ugo De Giorgi, Maha HA Hussain, Neal D.
Shore, et al.
PROSPER subgroup analysis by age and region: Overall survival and safety in men with nonmetastatic castration-resistant prostate cancer receiving androgen deprivation therapy plus enzalutamide.
2021 ASCO- GU.
Abstract 84.
Maha HA Hussain,Cora N.
Sternberg,Eleni Efstathiou,et al.
Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).
2021 ASCO-GU.
Abstract 94.
