a prospective randomized trial n. mottet, m peneau, jj mazeron, v molinié and p richaud
DESCRIPTION
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. Disclosures. N. Mottet: Advisor and paid consultant for Takeda - PowerPoint PPT PresentationTRANSCRIPT
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
Disclosures
N. Mottet: Advisor and paid consultant for TakedaReceived 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
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.
STUDY PROTOCOLSTUDY POPULATION
Age < 80, Karnofsky over 70Prostate Cancer histologically confirmedT3/T4 or pT3 ( biopsy) N0/M0Never treated except TURP for obstructive syndrome
PRIMARY ENDPOINT5 years overall Progression free survival:
biological and clinicalExpected benefit: 15% at 5 years
SECONDARY CRITERIASurvival (Overall and specific)Quality of life (QLQ-c30 and QLQ-PR25)Tolerance to treatment (SOMALENT)
STUDY DESIGN
M0aSelection
R1 R2
M0brandomization
2 months
R1 – M0b < 90 days
Centralized PSA (Hybritech) / 6 months Acute toxicity RTOG: M6
M6 M12 M18 M24 M30
M6 M12 M18 M24 M30 M36
V3,5 V4 V4,5V5
V3,5 V4 V4,5V5
Post protocolfollow-up
Treatment period : 3 years (ADT)(1 visit / 6 months)
Without treatment period : 2 years
(1 visit / 6 months)
M36
TREATMENT • ADT: Leuprorelin SR 11.25 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
POPULATION
Included patientsN=273
ITT Population N=263
ADT groupN=130
Combined groupN=133
Randomised patientsN=264
ADT groupN=131
Combined groupN=133
PP PopulationN=237
ADT groupN=128
Combined groupN=109
Planed number of patients = 25640 French sites
From March 2000 to December 2008 LVLP
Inclusion: 2000 – 2003Data base locked: 07/2009
Median follow up: 67 months
ADT ADT+RT
N 130 133
Mean Age , year (SD) 70.47 (5.64) 70.71 (5.66)
KARNOFSKI mean (SD) 96.11 (5.89) 96.62 (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 (%)
51.7738.2 %39.7 %22.1 %
41.535.3 %41.4 %23.3 %
Testosterone mean (SD) ng/ml 4.56 (1.84) 4.50 (1.72)
PATIENTS
Median PFS: 7.7 vs 1.7 years p < 0.0001
RESULTS 1 5 years overall PFS (ASTRO definition)
ADT group
Combined group
% p
atie
nts
Years
ADT group
Combined group
ADT group
Combined group
Median PFS: 6.96 vs 3.46 years p = 0.0005
RESULTS 2 5 years overall PFS (Phoenix definition)
ADT group
Combined group
% p
atie
nts
Years
ADT group
Combined group
PFS AND BASELINE PSA (Phoenix
definition )
RR : 5.22 [3.05; 8.95]; p=0.0011
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 2 3 4 5
Baseline PSA<20 ng/ml: ADT group combined group
p=0.001
Baseline 20<PSA<50 ng/ml: ADT group combined group
p = 0.0053
Baseline PSA>=50 ng/ml: ADT groupcombined group
% p
atie
nts
CLINICAL PFS ITT population
88.7% vs 62.3% p < 0.001
ADT group
Combined group
% p
ati
ents
ADT group
Combined group
Years
LOCO-REGIONAL PFS ITT population
90.3% vs 70.77% p < 0.0002
RR : 3.7 [1.9; 7.4] p<0.0002
% p
atie
nts ADT group
Combined group
ADT group
Combined group
Years
97% vs 89.23% p = 0.0183
METASTATIC PFS ITT population
% p
atie
nts
ADT group
Combined group
ADT group
Combined group
Years
OVERALL SURVIVAL ITT
population
At 5 years: 71.5% vs 71.4% p = 0.7882
ADT group
Combined group
% p
ati
ents
ADT group
Combined group
Years
SPECIFIC SURVIVAL ITT population
At 5 years: 93.2% vs 86.1% p = 0.11
% p
atie
nts
ADT group
Combined group
ADT group
Combined group
Years
% p
atie
nts
Years
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
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.