1. A prospective randomized trial
RADIOTHERAPY COMBINED WITH ANDROGEN DEPRIVATION (ADT) vs ADT IN CLINICALLY LOCALLY ADVANCED PROSTATE CANCER
A prospective randomized trial
N. Mottet, M Peneau, JJ Mazeron, V Molinié and P Richaud

2. Disclosures Protocol fully funded by Takeda France
N. Mottet: Advisor and paid consultant for Takeda
Received compensations for lectures and clinical trials
Protocol fully funded by Takeda France
Protocol independently written from the company
Data monitoring and statistical analysis performed by Mapi
An IDMC committee had full access to all data

3. BACKGROUND
Radiotherapy with prolonged ADT: superior to radiotherapy alone [EORTC 22863, 22961, RTOG 8531, 9202]
ADT: sometimes used alone in locally advanced PCa.
However - Combined modality superior to ADT (NSAA) [Widmark Lancet 2009]
- No data available with an LHRH agonist
Rational for a randomized trial: 3 years ADT ± Radiotherapy.

4. STUDY PROTOCOL Age < 80, Karnofsky over 70 STUDY POPULATION
Prostate Cancer histologically confirmed
T3/T4 or pT3 ( biopsy) N0/M0
Never treated except TURP for obstructive syndrome
PRIMARY ENDPOINT
5 years overall Progression free survival: biological and clinical
Expected benefit: 15% at 5 years
SECONDARY CRITERIA
Survival (Overall and specific)
Quality of life (QLQ-c30 and QLQ-PR25)
Tolerance to treatment (SOMALENT)

5. Treatment period : 3 years (ADT)
STUDY DESIGN
R1 – M0b < 90 days
Treatment period : 3 years (ADT)
(1 visit / 6 months)
Without treatment
period : 2 years
(1 visit / 6 months)
Post protocol
follow-up R1 R2
2 months M6
M12
M18
M24
M30
M36 V V V V
3,5 4
4,5 5
M0b
randomization
M0a
Selection M6
M12
M18
M24
M30
M36 V V V V
3,5 4
4,5 5
Centralized PSA (Hybritech) / 6 months Acute toxicity RTOG: M6

6. TREATMENT
ADT: Leuprorelin SR mg SC / 3 months + Flutamide 750 mg / day, Month 1
Radiotherapy : Total dose 70 ± 4 Gy. 35 fractions (±2) Pelvis (4 fields technique) 48 ± 2 Gy Prostate boost: 3D conformal
Standardized planning
OF NOTE
Radiotherapy quality control: independent committee validated each treatment
Independent Data monitoring committee

7. POPULATION
Planed number of patients = 256
40 French sites From March 2000 to December 2008 LVLP Inclusion: 2000 – 2003 Data base locked: 07/2009 Median follow up: 67 months
Included patients
N=273
Randomised patients
N=264
ADT group
N=131
Combined group
N=133
ITT Population
N=263
ADT group
N=130
Combined group
N=133
PP Population
N=237
ADT group
N=128
Combined group
N=109

8. PATIENTS ADT ADT+RT N 130 133 Mean Age , year (SD) 70.47 (5.64)
(5.64)
(5.66)
KARNOFSKI mean (SD)
(5.89)
(5.06)
GLEASON (SD)
< 7 (%)
≥ 7 (%)
6.4 ( 1.28)
51.9 %
48.1 %
6.6 (1.25)
45.9 %
54.1 %
T3N0M0 (%)
93.1 %
92.5 %
PSA (ng/ml) mean
< 20 (%)
20 – 50 (%)
≥ 50 (%)
51.77
38.2 %
39.7 %
22.1 %
41.5
35.3 %
41.4 %
23.3 %
Testosterone mean (SD) ng/ml
4.56 (1.84)
4.50 (1.72)
Score Gleason moyen initial: 6,4. Après relecture: 7,3

9. RESULTS 1 5 years overall PFS (ASTRO definition)
% patients
Years
ADT group
Combined group
ADT group
Combined group
ADT group
Combined group
Median PFS: 7.7 vs 1.7 years p <

10. RESULTS 2 5 years overall PFS (Phoenix definition)
ADT group
Combined group
% patients
Years
ADT group
Combined group
Median PFS: 6.96 vs 3.46 years p =

11. PFS AND BASELINE PSA (Phoenix definition )
100%
Baseline PSA<20 ng/ml: ADT group combined group
p=0.001
Baseline 20<PSA<50 ng/ml: ADT group combined group
p =
Baseline PSA>=50 ng/ml: ADT group combined group
90%
80%
70%
60%
50%
% patients
40%
30%
20%
RR : 5.22 [3.05; 8.95]; p=0.0011
10% 0% 1 2 3 4 5

12. CLINICAL PFS ITT population
ADT group
Combined group
% patients
Years
ADT group
Combined group
88.7% vs 62.3% p < 0.001

13. LOCO-REGIONAL PFS ITT population
ADT group
Combined group
% patients
RR : 3.7 [1.9; 7.4] p<0.0002
Years
ADT group
Combined group
90.3% vs 70.77% p <

14. METASTATIC PFS ITT population
ADT group
Combined group
% patients
Years
ADT group
Combined group
97% vs 89.23% p =

15. OVERALL SURVIVAL ITT population
ADT group
Combined group
% patients
Years
ADT group
Combined group
At 5 years: 71.5% vs 71.4% p =

16. SPECIFIC SURVIVAL ITT population
ADT group
Combined group
% patients
% patients
Years
Years
ADT group
Combined group
At 5 years: 93.2% vs 86.1% p = 0.11

17. SUMMARY
In patients with locally advanced PCa, addition of local radiotherapy to 3 years of LHRH significantly reduces the progression risk (biological, clinical, metastatic).
The benefit appears to be related mainly to improved loco-regional control.
A prolonged follow up is needed to see a potential survival impact

18. CONCLUSION
This reduction of disease progression confirms that radiotherapy combined with ADT should be one standard for patients with a locally advanced disease and a significant life expectancy.