Alessio Crippa
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet
Changes in the parameters of the simulation design
Updated results
ARA DRD TP53 TEfus prev
1 - - - - 0.3238
2 - - - + 0.0667
3 - - + - 0.1714
4 - - + + 0.1143
5 - + - - 0.0667
6 - + - + 0.0476
7 - + + - 0.0190
8 - + + + 0.0095
9 + - - - 0.0476
10 + - - + 0.0381
11 + - + - 0.0095
12 + - + + 0.0381
13 + + - - 0.0286
14 + + - + 0.0095
15 + + + - 0.0095
signatures ---- ---+ --+- --++ -+-- -+-+ -++- -+++ +--- +--+ +-+- +-++ ++-- ++-+ +++- n prev
1 all X X X X X X X X X X X X X X X 105 1.00
2 TP53- & AR- X X X X 53 0.50
3 TP53+ | AR+ X X X X X X X X X X X 52 0.50
4 DRD+ X X X X X X X 20 0.19
5 DRD- X X X X X X X X 85 0.81
6 TEfus+ X X X X X X X 34 0.32
7 TEfus- X X X X X X X X 71 0.68
\( T_{ixk} \sim Weibull(\textrm{shape} = 2, \textrm{scale}_{xk}) \)
\( i = 1, \dots, n_{xk}, \;\; \) \( x = 2, \dots, 6 \; \) \( k = 1, \dots, 15 \)
Mean PFS: 3.5 months for an ineffective treatment (median 3.3)
Mean PFS: 7.1 months for an effective treatment, HR: 2 (median 6.7)
Waiting for more data
True mean PF times
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
---- 3.5 3.5 3.5 3.5 3.5
---+ 3.5 3.5 3.5 3.5 3.5
--+- 3.5 3.5 3.5 3.5 3.5
--++ 3.5 3.5 3.5 3.5 3.5
-+-- 3.5 3.5 3.5 3.5 3.5
-+-+ 3.5 3.5 3.5 3.5 3.5
-++- 3.5 3.5 3.5 3.5 3.5
-+++ 3.5 3.5 3.5 3.5 3.5
+--- 3.5 3.5 3.5 3.5 3.5
+--+ 3.5 3.5 3.5 3.5 3.5
+-+- 3.5 3.5 3.5 3.5 3.5
+-++ 3.5 3.5 3.5 3.5 3.5
++-- 3.5 3.5 3.5 3.5 3.5
++-+ 3.5 3.5 3.5 3.5 3.5
+++- 3.5 3.5 3.5 3.5 3.5
Average Number of Participants by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 144 144 146 144 145
TP53- & AR- 75 75 74 74 74
TP53+ | AR+ 69 69 72 70 71
DRD+ 36 37 37 36 37
DRD- 108 107 109 108 108
TEfus+ 46 46 49 47 47
TEfus- 98 98 97 98 98
Graduation Probabilities
p1 p2
Enzalutamide 0 0.040
Abiraterone 0 0.020
Radium.223 0 0.020
Cabazitaxel 0 0.020
Docetaxel 0 0.045
Graduation Times by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 24 24 24 24 24
TP53- & AR- 24 24 24 24 24
TP53+ | AR+ 24 24 24 24 24
DRD+ 24 24 24 24 24
DRD- 24 24 24 24 24
TEfus+ 24 24 24 24 24
TEfus- 24 24 24 24 24
Probability of superiority by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.060 0.061 0.059 0.061 0.060
TP53- & AR- 0.157 0.169 0.156 0.163 0.160
TP53+ | AR+ 0.098 0.098 0.097 0.098 0.095
DRD+ 0.156 0.160 0.164 0.164 0.159
DRD- 0.097 0.100 0.092 0.096 0.093
TEfus+ 0.136 0.140 0.135 0.138 0.133
TEfus- 0.119 0.122 0.117 0.122 0.119
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.00 0.000 0.000 0.000 0.000
TP53- & AR- 0.04 0.020 0.010 0.015 0.030
TP53+ | AR+ 0.00 0.000 0.000 0.000 0.000
DRD+ 0.00 0.000 0.000 0.000 0.000
DRD- 0.00 0.005 0.015 0.000 0.015
TEfus+ 0.00 0.000 0.000 0.000 0.000
TEfus- 0.00 0.000 0.005 0.005 0.005
True mean PF times
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
---- 3.5 7.1 3.5 3.5 3.5
---+ 3.5 7.1 3.5 3.5 3.5
--+- 3.5 7.1 3.5 3.5 3.5
--++ 3.5 7.1 3.5 3.5 3.5
-+-- 3.5 7.1 3.5 3.5 3.5
-+-+ 3.5 7.1 3.5 3.5 3.5
-++- 3.5 7.1 3.5 3.5 3.5
-+++ 3.5 7.1 3.5 3.5 3.5
+--- 3.5 7.1 3.5 3.5 3.5
+--+ 3.5 7.1 3.5 3.5 3.5
+-+- 3.5 7.1 3.5 3.5 3.5
+-++ 3.5 7.1 3.5 3.5 3.5
++-- 3.5 7.1 3.5 3.5 3.5
++-+ 3.5 7.1 3.5 3.5 3.5
+++- 3.5 7.1 3.5 3.5 3.5
Average Number of Participants by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 149 78 150 150 151
TP53- & AR- 78 43 76 77 76
TP53+ | AR+ 71 35 75 74 75
DRD+ 40 17 41 40 41
DRD- 109 62 109 110 109
TEfus+ 49 23 51 50 51
TEfus- 100 55 99 100 99
Graduation Probabilities
p1 p2
Enzalutamide 0.00 0.000
Abiraterone 0.69 0.000
Radium.223 0.00 0.000
Cabazitaxel 0.00 0.005
Docetaxel 0.00 0.000
Graduation Times by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 24 11.3 24 24 24
TP53- & AR- 24 19.7 24 24 24
TP53+ | AR+ 24 23.6 24 24 24
DRD+ 24 23.9 24 24 24
DRD- 24 7.9 24 24 24
TEfus+ 24 23.7 24 24 24
TEfus- 24 14.2 24 24 24
Probability of superiority by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.017 0.84 0.015 0.015 0.015
TP53- & AR- 0.065 0.90 0.059 0.052 0.057
TP53+ | AR+ 0.047 0.66 0.043 0.044 0.044
DRD+ 0.116 0.51 0.104 0.103 0.106
DRD- 0.026 0.92 0.025 0.024 0.026
TEfus+ 0.077 0.69 0.066 0.071 0.071
TEfus- 0.049 0.81 0.048 0.044 0.045
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0 0.695 0 0.000 0
TP53- & AR- 0 0.300 0 0.005 0
TP53+ | AR+ 0 0.025 0 0.000 0
DRD+ 0 0.030 0 0.000 0
DRD- 0 0.880 0 0.000 0
TEfus+ 0 0.030 0 0.000 0
TEfus- 0 0.545 0 0.000 0
True mean PF times
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
---- 3.5 7.1 3.5 3.5 3.5
---+ 3.5 7.1 3.5 3.5 3.5
--+- 3.5 3.5 3.5 3.5 3.5
--++ 3.5 3.5 3.5 3.5 3.5
-+-- 3.5 7.1 3.5 3.5 3.5
-+-+ 3.5 7.1 3.5 3.5 3.5
-++- 3.5 3.5 3.5 3.5 3.5
-+++ 3.5 3.5 3.5 3.5 3.5
+--- 3.5 3.5 3.5 3.5 3.5
+--+ 3.5 3.5 3.5 3.5 3.5
+-+- 3.5 3.5 3.5 3.5 3.5
+-++ 3.5 3.5 3.5 3.5 3.5
++-- 3.5 3.5 3.5 3.5 3.5
++-+ 3.5 3.5 3.5 3.5 3.5
+++- 3.5 3.5 3.5 3.5 3.5
Average Number of Participants by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 150 114 148 147 148
TP53- & AR- 78 55 75 75 76
TP53+ | AR+ 72 59 74 72 72
DRD+ 39 22 40 39 39
DRD- 110 92 109 109 109
TEfus+ 50 39 49 48 48
TEfus- 99 75 99 99 100
Graduation Probabilities
p1 p2
Enzalutamide 0.0 0.015
Abiraterone 0.9 0.085
Radium.223 0.0 0.010
Cabazitaxel 0.0 0.010
Docetaxel 0.0 0.015
Graduation Times by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 24 22.2 24 24 24
TP53- & AR- 24 9.6 24 24 24
TP53+ | AR+ 24 24.0 24 24 24
DRD+ 24 24.0 24 24 24
DRD- 24 18.8 24 24 24
TEfus+ 24 24.0 24 24 24
TEfus- 24 17.3 24 24 24
Probability of superiority by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.032 0.40 0.033 0.030 0.033
TP53- & AR- 0.058 0.92 0.058 0.052 0.057
TP53+ | AR+ 0.089 0.13 0.095 0.089 0.094
DRD+ 0.124 0.34 0.136 0.119 0.138
DRD- 0.056 0.52 0.053 0.055 0.051
TEfus+ 0.117 0.34 0.110 0.100 0.104
TEfus- 0.064 0.51 0.076 0.072 0.077
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.000 0.10 0.000 0.00 0.000
TP53- & AR- 0.010 0.90 0.005 0.01 0.010
TP53+ | AR+ 0.000 0.00 0.000 0.00 0.000
DRD+ 0.000 0.00 0.000 0.00 0.000
DRD- 0.000 0.29 0.005 0.00 0.000
TEfus+ 0.000 0.00 0.000 0.00 0.000
TEfus- 0.005 0.39 0.000 0.00 0.005
True mean PF times
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
---- 7.1 7.1 3.5 3.5 3.5
---+ 7.1 7.1 3.5 3.5 7.1
--+- 3.5 3.5 3.5 3.5 3.5
--++ 3.5 3.5 3.5 3.5 7.1
-+-- 7.1 7.1 3.5 3.5 3.5
-+-+ 7.1 7.1 3.5 3.5 7.1
-++- 3.5 3.5 3.5 3.5 3.5
-+++ 3.5 3.5 3.5 3.5 7.1
+--- 3.5 3.5 3.5 3.5 3.5
+--+ 3.5 3.5 3.5 3.5 7.1
+-+- 3.5 3.5 3.5 3.5 3.5
+-++ 3.5 3.5 3.5 3.5 7.1
++-- 3.5 3.5 3.5 3.5 3.5
++-+ 3.5 3.5 3.5 3.5 7.1
+++- 3.5 3.5 3.5 3.5 3.5
Average Number of Participants by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 129 130 152 150 152
TP53- & AR- 64 64 75 72 69
TP53+ | AR+ 65 65 77 78 82
DRD+ 26 25 42 41 45
DRD- 104 105 110 109 107
TEfus+ 37 38 54 55 59
TEfus- 92 92 98 95 93
Graduation Probabilities
p1 p2
Enzalutamide 0.92 0.005
Abiraterone 0.90 0.020
Radium.223 0.00 0.000
Cabazitaxel 0.00 0.000
Docetaxel 0.78 0.020
Graduation Times by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 24.0 23.9 24 24 24
TP53- & AR- 9.2 9.7 24 23 23
TP53+ | AR+ 24.0 24.0 24 24 24
DRD+ 24.0 24.0 24 24 24
DRD- 23.4 23.8 24 24 24
TEfus+ 24.0 24.0 24 24 14
TEfus- 22.6 22.1 24 24 24
Probability of superiority by Signature
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.175 0.168 0.0060 0.0052 0.429
TP53- & AR- 0.682 0.692 0.0103 0.0064 0.337
TP53+ | AR+ 0.068 0.059 0.0503 0.0513 0.504
DRD+ 0.252 0.252 0.0809 0.0688 0.335
DRD- 0.238 0.218 0.0096 0.0114 0.566
TEfus+ 0.145 0.131 0.0275 0.0253 0.873
TEfus- 0.388 0.388 0.0396 0.0369 0.061
Enzalutamide Abiraterone Radium 223 Cabazitaxel Docetaxel
all 0.000 0.005 0 0 0.000
TP53- & AR- 0.925 0.895 0 0 0.055
TP53+ | AR+ 0.000 0.000 0 0 0.010
DRD+ 0.000 0.000 0 0 0.000
DRD- 0.035 0.015 0 0 0.015
TEfus+ 0.000 0.000 0 0 0.780
TEfus- 0.080 0.110 0 0 0.000