Prostate cancer: TROPIC trial

Abbreviations

No EU-CTR

  • TROPIC references
    2010-10-02
    J.S. de Bono
    Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment
Investigated (inv)
Comparator (comp)

CABA+pred+ADT

mitox+pred+ADT

378

377

Phase:

3

Randomisation:

Open label

Primary tumour:

Prostate

Subtype (biomarker):

mCRPC

Stage:

meta

Line of therapy:

L2

Primary
CABA+pred+ADT
mitox+pred+ADT
HR
p
OS
15.1 mo
12.7 mo
0.70 (0.59-0.83)
<0.0001
Secondaries
CABA+pred+ADT
mitox+pred+ADT
HR
p
PFS
2.8 mo
1.4 mo
0.74 (0.64-0.86)
<0.001
PSA response %
39.2%
17.8%
0.0002
Pain response %
9.2%
7.7%
0.63
time to PSA progression
6.4 mo
3.1 mo
0.75 (0.63-0.90)
0.001
(all grades, %)
CABA+pred+ADT
mitox+pred+ADT
p
neutropenia (≥3)
82
58
NA
diarrhoea (≥3)
6
<1
NA
febrile neutropenia (≥3)
8
1
NA
Leukopenia (≥3)
68
42
NA
Anaemia (≥3)
11
5
NA
Thrombocytopenia (≥3)
4
2
NA
Fatigue
37
27
NA
Haematuria
17
4
NA
Nausea
34
23
NA
Abdominal pain
12
4
NA
Vomiting
23
10
NA
Dyspnoea
12
5
NA
Constipation
20
15
NA
Pyrexia
12
6
NA
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed adenocarcinoma of the prostate that is refractory to hormone therapy and previously treated with a Taxotere®-containing regimen. - Documented progression of disease (demonstrating at least one visceral or soft tissue metastatic lesion, including a new lesion). - Patients with non-measurable disease must have documented rising prostate-specific antigen (PSA) levels or appearance of new lesion. - Surgical or hormone-induced castration - Life expectancy > 2 months - ECOG performance status 0 - 2

- Previous treatment with mitoxantrone - Previous treatment with <225 mg/m^2 cumulative dose of Taxotere (or docetaxel) - Prior radiotherapy to ≥ 40% of bone marrow - Surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study - Other prior malignancy, except for adequately treated superficial basal cell skin cancer, or any other cancer from which the patient has been disease-free for less than 5 years - Known brain or leptomeningeal involvement - Other concurrent serious illness or medical conditions - Inadequate organ function evidenced by unacceptable laboratory results

Characteristics
CABA+pred+ADT
mitox+pred+ADT
Age & ECOG performance status
Median (yr)
67 (61−72)
68 (62−73)
≥75
70 (19%)
69 (18%)
ECOG performance status 0 or 1
344 (91%)
350 (93%)
Extent of disease
Metastatic
356 (94%)
364 (96%)
Bone metastases
328 (87%)
303 (80%)
Visceral metastases
94 (25%)
94 (25%)
Locoregional recurrence
20 (5%)
14 (4%)
Previous therapy
Hormonal
375 (99%)
375 (99%)
1 chemotherapy regimen
268 (71%)
260 (69%)
2 chemotherapy regimens
79 (21%)
94 (25%)
>2 chemotherapy regimens
30 (8%)
24 (6%)
Previous therapy (cont.)
Radiation
222 (59%)
232 (61%)
Surgery
205 (54%)
198 (52%)
Biological agent
36 (10%)
26 (7%)
Number of previous docetaxel regimens
1
327 (87%)
316 (84%)
2
43 (11%)
53 (14%)
>2
7 (2%)
9 (2%)
Total previous docetaxel dose (mg/m2)
529.2 (380.9−787.2)
576.6 (408.4−761.2)
Disease progression (DP) relative to docetaxel administration
During treatment
104 (28%)
115 (30%)
<3 months from last dose
181 (48%)
158 (42%)
≥3 months from last dose
90 (24%)
102 (27%)
Median time from last docetaxel dose to DP (mo.)
0.7 (0.0−2.9)
0.8 (0.0−3.1)
PSA levels
Median serum PSA concentration (μg/L)
127.5 (44.0−419.0)
143.9 (51.1−416.0)
Serum PSA concentration ≥20 μg/L
325 (86%)
329 (87%)
Ethnic origin
White
314 (83%)
317 (84%)
Asian
32 (8%)
26 (7%)
Black
20 (5%)
20 (5%)
Other
11 (3%)
15 (4%)
Ad-hoc:
no.pts inv.
no.pts comp.
CABA+pred+ADT
mitox+pred+ADT
HR
p
ORR
201
204
14.4%
4.4%
0.0005
time to tumour progression
378
377
8.8 mo
5.4 mo
0.61 (0.49−0.76)
<0.0001
time to pain progression
378
377
11.1 mo
NR
0.91 (0.69-1.19)
0.52
  • OS
analisys of OS
CABA+pred+ADT
mitox+pred+ADT
HR (95% CI)
ECOG
0 - 1
0·68 (0·57–0·82)
2
0·81 (0·48–1·38)
No. of previous chemotherapies
1
0·67 (0·55–0·83)
≥2
0·75 (0·55–1·02)
Pain at baseline
Yes
0·77(0·61–0·98)
No
0·55 (0·42–0·72)
Rising PSA at baseline
Yes
0·65 (0·53–0·80)
No
0·88 (0·61–1·26)
Progression during docetaxel
<3 mo after docetaxel
0·70 (0·55–0·91)
≥3 mo after docetaxel
0·75 (0·51–1·11)
Total docetaxel dose
<225 mg/m2
0·96 (0·49–1·86)
≥225–450 mg/m2
0·60 (0·43–0·84)
Total docetaxel dose
≥450–675 mg/m2
0·83 (0·60–1·16)
≥900 mg/m2
0·51 (0·33–0·79)
Age
<65 yr
0.81 (0.61–1.08)
≥65 yr
0.62 (0.50–0.78)
Measurable disease
Yes
0.68 (0.54–0.85)
No
0.72 (0.55–0.93)
analisys of
CABA+pred+ADT
mitox+pred+ADT
HR (95% CI)