Introduction
Materials and methods
Patients and treatment
Objectives and statistics
Results
Detection rates at baseline
Mean | SD | Quantile 0% | Quantile 25% | Quantile 50% (median) | Quantile 75% | Quantile 100% | N | |
---|---|---|---|---|---|---|---|---|
CTC | 81.65 | 324.76 | 0 | 0 | 2.5 | 23.25 | 3,369 | 260 |
CA15.3 | 7.53 | 23.77 | 0.14 | 0.7 | 1.76 | 4.45 | 314.1 | 247 |
CEA | 7.20 | 18.23 | 0.04 | 0.4 | 1 | 3.45 | 146.13 | 212 |
CYFRA21 | 9.01 | 29.51 | 0.1 | 0.65 | 1.95 | 5.25 | 284.54 | 191 |
LDH | 1.39 | 2.02 | 0.28 | 0.71 | 0.92 | 1.45 | 25.54 | 220 |
ALP | 1.056 | 1.00 | 0.26 | 0.58 | 0.79 | 1.06 | 10 | 241 |
Patient characteristics | N patients assessed | CA 15-3 > ULNV | CEA > ULNV | CYFRA 21-1 > ULNV | LDH > ULNV | ALP > ULNV | CTC ≥ 5 |
---|---|---|---|---|---|---|---|
Menopausal status
| NS | NS |
P
= 0.01
| NS | NS | NS | |
Premenopausal
| 113 | 42% | 44% |
54%
| 44% | 25% | 45% |
Postmenopausal
| 148 | 58% | 56% |
72%
| 45% | 33% | 43% |
Receptor status
| NS |
P
= 0.002
| NS | NS | NS | NS | |
Horm. positive
| 159 | 68% |
58%
| 65% | 40% | 33% | 46% |
HER2 positive
| 45 | 60% |
51%
| 56% | 49% | 32% | 34% |
Triple negative
| 54 | 57% |
27%
| 74% | 53% | 19% | 46% |
Tumor grade
| NS |
P
= 0.05
| NS | NS |
P
= 0.03
| NS | |
1
| 26 | 77% |
76%
| 64% | 37% |
52%
| 48% |
2
| 106 | 64% |
55%
| 62% | 43% |
28%
| 41% |
3
| 123 | 63% |
45%
| 68% | 47% |
25%
| 45% |
Performance status
|
P
= 0.003
|
P
= 0.02
|
P
< 10
-4
|
P
< 10
-4
|
P
= 0.001
|
P
< 10
-4
| |
0
| 123 |
55%
|
42%
|
51%
|
21%
|
18%
|
29%
|
1
| 97 |
69%
|
57%
|
70%
|
58%
|
34%
|
49%
|
2
| 22 |
82%
|
53%
|
79%
|
79%
|
52%
|
71%
|
3 or 4
| 13 |
92%
|
78%
|
100%
|
100%
|
54%
|
92%
|
Number of metastatic sites
|
P
= 0.02
| NS |
P
= 0.001
|
P
< 10
-4
| NS |
P
= 0.03
| |
< 3
| 155 |
60%
| 52% |
55%
|
37%
| 28% |
39%
|
≥ 3
| 106 |
71%
| 51% |
80%
|
56%
| 31% |
48%
|
CA 15.3
| - |
P
< 10
-4
|
P
< 10
-4
|
P
< 10
-4
|
P
< 10
-4
|
P
< 10
-4
| |
≤ ULNV
| 88 | - |
24%
|
54%
|
25%
|
13%
|
26%
|
> ULNV
| 159 | - |
68%
|
72%
|
56%
|
40%
|
53%
|
CEA
| - | - |
P
= 0.005
|
P
= 0.009
|
P
= 0.001
|
P
= 0.03
| |
≤ ULNV
| 103 | - | - |
56%
|
36%
|
18%
|
35%
|
> ULNV
| 109 | - | - |
75%
|
55%
|
38%
|
49%
|
CYFRA 21-1
| - | - | - |
P
< 10
-4
| NS |
P
< 10
-4
| |
≤ ULNV
| 66 | - | - | - |
16%
| 23% |
19%
|
> ULNV
| 125 | - | - | - |
63%
| 34% |
56%
|
LDH
| - | - | - | - |
P
= 0.02
|
P
< 10
-4
| |
≤ ULNV
| 121 | - | - | - | - |
22%
|
25%
|
> ULNV
| 99 | - | - | - | - |
36%
|
67%
|
ALP
| - | - | - | - | - |
P
< 10
-4
| |
≤ ULNV
| 170 | - | - | - | - | - |
36%
|
> ULNV
| 71 | - | - | - | - | - |
65%
|
All population
at baseline
| 64% | 51% | 65% | 45% | 29% | 44% | |
All population
before cycle 2
| 66% | 46% | 34% | 43% | 28% | 17% | |
All population
before cycle 3/4
| 64% | 40% | 27% | 49% | 22% | 13% |
Markers assessed | N patients assessed | % with at least 1 elevated marker | |||
---|---|---|---|---|---|
CEA | CA 15-3 | CYFRA 21-1 | CTC | ||
2 markers combinations
| |||||
X
| X | 239 | 72% | ||
X
| X | 240 | 75% | ||
X | X | 257 | 75% | ||
X | X | 225 | 77% | ||
X
| X | 206 | 80% | ||
X | X | 231 | 86% | ||
3 markers combinations
| |||||
X
| X | X | 251 | 83% | |
X
| X | X | 233 | 86% | |
X
| X | X | 234 | 88% | |
X | X | X | 234 | 88% | |
4 markers combination
| |||||
X
| X | X | X | 246 | 90% |
Single assessment and association with PFS
Variable | Univariate | Multiv clin | Multiv clin + CTC | Multiv clin + CA 15.3 | Multiv clin + CYFRA 21 | Multiv clin + CEA | Multiv clin + LDH | Multiv clin + ALP |
---|---|---|---|---|---|---|---|---|
Triple neg. | 3.05 (2.14; 4.36) | 3.55 (2.43; 5.18) | 3.33 (2.06; 5.39) | 3.27 (2.03; 5.30) | 3.14 (1.95; 5.06) | 4.417 (2.628; 7.425) | 3.061 (1.89; 4.95) | 3.344 (2.062; 5.423) |
PS > 0
| 2.30 (1.65; 3.21) | 2.659 (1.89; 3.741) | 2.097 (1.319; 3.33) | 2.359 (1.509; 3.69) | 2.133 (1.35; 3.36) | 2.428 (1.56; 3.78) | 1.968 (1.21; 3.19) | 2.49 (1.58; 3.93) |
Nb of metastatic sites > 2
| 1.886 (1.378; 2.581) | NS | ||||||
CTC ≥ 5
| 2.263 (1.644; 3.115) | 1.996 (1.277; 3.122) | ||||||
CA15-3 ≥ ULNV
| 1.665 (1.167; 2.374) | 1.746 (1.095; 2.783) | ||||||
CYFRA 21-1 ≥ ULNV
| 2.901 (1.896; 4.439) | 2.097 (1.27; 3.46) | ||||||
CEA ≥ ULNV
| 1.64 (1.151; 2.337) | 2.015 (1.272; 3.191) | ||||||
LDH ≥ ULNV
| 2.525 (1.781; 3.579) | 1.933 (1.203; 3.104) | ||||||
ALP ≥ ULNV
| 1.501 (1.058; 2.131) | 1.108 (0.684; 1.793) | ||||||
C-INDEX
| 0.697 (0.65; 0.75) | 0.71 (0.663; 0.767) | 0.713 (0.661; 0.765) | 0.723 (0.68; 0.77) | 0.714 (0.664; 0.765) | 0.717 (0.668; 0.766) | 0.688 (0.637; 0.74) |