Paris- RP Reims Rennes Tours Marseille Montpellier Lyon Nice Lille Strasbourg Bordeaux Dijon Besançon Nantes Toulouse Poitiers Angers Nancy Caen Rouen.

Paris- RPReims

RennesTours

MarseilleMontpellier

Lyon

Nice

Lille

Strasbourg

Bordeaux

DijonBesançon

Nantes

Toulouse

Poitiers

Angers

Nancy

Caen

Rouen

Clermont-Ferrand

GSF: Groupe Sarcome FrançaisGSF: Groupe Sarcome FrançaisGETO: Groupe d’Etudes des Tumeurs OsseusesGETO: Groupe d’Etudes des Tumeurs Osseuses

VillejuifN = 36 institutionsN = 36 institutions

Sarcoma Database:Sarcoma Database:3300 pts3300 pts

Frozen tissue bank:Frozen tissue bank:1300 sarcomas1300 sarcomas

Sarcome 01 Sarcome 01 Euro-Ewing 99Euro-Ewing 99PI :PI : Dr O. Oberlin – VillejuifDr O. Oberlin – Villejuif

EORTCEORTC SFCESFCE GPOHGPOH UKCCSGUKCCSG TotalTotal

NN 567567 18741874

Molecular analysis on Iry: 448 patients (79 %)BM: 326 patients (57%)

30 sept 0630 sept 06

Suspension of R1 randomizationSuspension of R1 randomization0

100

200

300

400

500

600

1 11 21 31 41 51 61 71 81

Patients prévus

Patients inclus

567

525

Sarcome 02 Sarcome 02 PALSAR IIPALSAR II

PI :PI : Dr N B BUI – BordeauxDr N B BUI – Bordeaux

Arm 1 2 MAID

RA

ND

OM

ISA

TIO

N

4 MAID

SD / RP/ RC +/- surgery

PD

Arm 2 1 MAID – MICE + PBSC

Main end-point: Main end-point: overall survivaloverall survivalStatistical hypothesis: Statistical hypothesis: 3-yr OS: 40% vs 15% (N® per arm: 50)3-yr OS: 40% vs 15% (N® per arm: 50)

October 06: October 06: N = 207 patientsN = 207 patients N® = 65/100 patientsN® = 65/100 patients

Sarcome 03 Sarcome 03 OsteosarcomaOsteosarcoma

PI :PI : A Le Cesne – VillejuifA Le Cesne – Villejuif

Localized operableosteosarcoma

API-AI regimen4 CT courses

Main end-point: Main end-point: histological response ratehistological response rate

Good histological response: Good histological response: 37%37% ASCO 06ASCO 062-yr overall survival:2-yr overall survival: 86% 86% 2-yr PFS2-yr PFS 74%74%

Follow-upFollow-up

Inclusion Curve

40

47

0

5

10

15

20

25

30

35

40

45

50

Nu

mb

er o

f p

atie

nts

Theoric

Real

Sarcome 04 Sarcome 04 EWINGEWING

PI :PI : O Oberlin – VillejuifO Oberlin – Villejuif

D1 D8 D15D1 D8 D15 D21 D21 D28/1 D8 D15 D21 D28 D28/1 D8 D15 D21 D28

CDDPCDDP

VP-16VP-16

Main end-point: Main end-point: Objective response rateObjective response rateStatistical hypothesis: Statistical hypothesis: Simon: at least 6/29 OR Simon: at least 6/29 OR

October 2006 = 44/45October 2006 = 44/45ASCO 07ASCO 07

Sarcome 05 Sarcome 05 DesminibDesminib

PI :PI : JY Blay – LyonJY Blay – Lyon

Progressive AF/Desmoid TGlivec®: 400 mg/d800 mg/d if PDDuration: one year

Main end-point: Main end-point: 3-month PFS (at least 7 patients not PD)3-month PFS (at least 7 patients not PD)At 3 month: At 3 month: 1 CR, 1 PR, 31 SD, 5 PD 1 CR, 1 PR, 31 SD, 5 PD ASCO 06ASCO 066-m PFS 73%; 1-yr PFS 69%6-m PFS 73%; 1-yr PFS 69%Translational research ongoingTranslational research ongoing

imatinibimatinibRandomRandom

NSAIDNSAID

courbes des inclusions

0

5

10

15

20

25

30

35

40

45

août-

04

oct-

04

déc-0

4

févr-

05

avr-

05

juin

-05

août-

05

oct-

05

déc-0

5

févr-

06

avr-

06

juin

-06

août-

06

oct-

06

déc-0

6

févr-

07

avr-

07

juin

-07

août-

07

No

mb

re d

e p

ati

en

ts

Théorique

Réelle

40 39

Sarcome 06: Sarcome 06: AngiotaxAngiotax

PI :PI : N Penel – LilleN Penel – Lille

AngiosarcomaAngiosarcoma2nd/3rd CT line2nd/3rd CT line

Weekly taxol: 80 mg/wWeekly taxol: 80 mg/w3 weeks on, 1 off3 weeks on, 1 off

Main end-point: Main end-point: Objective response rateObjective response rateStatistical hypothesis: Statistical hypothesis: Simon two step: 15 + 10 patientsSimon two step: 15 + 10 patients

at least 6/25 OR at least 6/25 OR Secondary end-point: Secondary end-point: PFS, OS, tolerancePFS, OS, toleranceTranslational researchTranslational research

ASCO 2007ASCO 2007

courbes des inclusions

0

5

10

15

20

25

30

35

Théorique

Réelle

30 30

Sarcome 07 Sarcome 07 TaxogemTaxogem

PI :PI : F. Duffaud – MarseilleF. Duffaud – MarseilleP. Pautier - VillejuifP. Pautier - Villejuif

® phase II® phase IILeiomyosarcomaLeiomyosarcoma

Uterine vs otherUterine vs other2nd CT line2nd CT line

N = 40 + 40N = 40 + 40

Main end-point: Main end-point: ORORSecondary end-point: Secondary end-point: PFS, OS, tolerance, QOLPFS, OS, tolerance, QOL

N = 13/80N = 13/80

Gemzar. n°1

Gemzar n°2

Gemzar n°3

Randomisation

Gemzar

J1 J8 J15

J22 J1=J29

J1 J8

BRAS A

BRAS B

Granocyte J9-J15

J15

CYCLE N CYCLE N+1

Gemzar + TXT

J1=J22

PI (FSG) :PI (FSG) : A Le Cesne – VillejuifA Le Cesne – Villejuif

Sarcome 08:Sarcome 08:Adjuvant GISTAdjuvant GISTEORTC 62024EORTC 62024

October 2006October 2006N = 418 N = 418

No adjuvantG livec

G livec400m g/j 2 years

R andom ization

G IST CD117+Definitive surgery

Participating French centers : 42Participating French centers : 42Mutational analysis: 70%Mutational analysis: 70%

Courbe des inclusions

0

20

40

60

80

100

120

140

Mois

No

mb

re d

e p

atie

nts

Théorique

Réelle

100127

0

2

4

6

8

10

12

14

16

18

20

Inclusions centres traités/non traités

non traité

traité

PI :PI : F Duffaud – Curie / L Brugieres - VillejuifF Duffaud – Curie / L Brugieres - Villejuif

Intergroup SFCE/GSF/GETOIntergroup SFCE/GSF/GETO Adult/children OS – phase III ZoledronateAdult/children OS – phase III Zoledronate

N = 470N = 4703-yr EFS > 13%3-yr EFS > 13%in exp armin exp arm

TranslationalTranslationalresearchresearch

Sarcome 09 Sarcome 09 OS 2006OS 2006

M T X - VP- I FO A PI - A I M T X - VP- I FO

Z ometa

M T X ou A PI

au choix

du centreA PI - A I

Z ometa

BR M R BR M R BR M R BR M R

M T XVP-IFO A PI VP-IFO

VP- I FO

Z ometa

M T X

VP- I FO

Z ometa

M T X

CP- A d

M T X

CP- A d

Z ometa

A PI

Z ometa

M T X ou A PI

au choix

du centre

<18 ans 18- 25 ans >25 ans

S ans Z ometa

<18 ans 18- 25 ans >25 ans

A vec Z ometa

Randomisat ion

PI:PI: P Pautier – VillejuifP Pautier – Villejuif

Uterine leiomyoS, carcinoS, high grade endometrial SUterine leiomyoS, carcinoS, high grade endometrial S

N = 52 / 256N = 52 / 2563-yr EFS > 20% in experimental arm3-yr EFS > 20% in experimental arm

Sarc-Gyn 1 Sarc-Gyn 1 Adjuvant CTAdjuvant CT

Arm AArm A

4 x API4 x API RTE 45 Gy RTE 45 Gy ++ Brachytherapy 15 Gy Brachytherapy 15 Gy

A (50), I ( 6), C (75)A (50), I ( 6), C (75)

Surgery < 6 wSurgery < 6 w RR

RTE 45 Gy RTE 45 Gy ++ Brachytherapy 15 Gy Brachytherapy 15 Gy- Arm BArm B

BFR 14 trial - BFR 14 trial - Advanced GISTAdvanced GIST (June 2002)(June 2002)

StopStop

Imatinib Imatinib Non PD RNon PD R

ImatinibImatinib

PI :PI : J.Y Blay – LyonJ.Y Blay – LyonA. Le Cesne - VillejuifA. Le Cesne - Villejuif

N patients included in October 2005:N patients included in October 2005: 271271

1) 1) N randomized (interrupted) pts at 1 year: 58 (ASCO 04,05)N randomized (interrupted) pts at 1 year: 58 (ASCO 04,05)

Stop imatinib arm:Stop imatinib arm: 3232imatinib arm:imatinib arm: 2626

2) 2) N randomized (ongoing) pts at 3 years:N randomized (ongoing) pts at 3 years: 32 (ASCO 07) 32 (ASCO 07)

BFR14 : Survie sans progression des randomisés à 1 an

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 6 12 18 24 30 36 42

Délai depuis randomisation à 1 an (mois)

Pro

ba

bil

ité

de

su

rv

ie

Log-rank test : p < 0.0001

CONT group10 evts / 26 patientsMédiane SSP: 28.3 moisSTOP group

28 evts / 32 patientsMédiane SSP : 6.1 mois

AB1010 first line - AB1010 first line - Advanced GISTAdvanced GIST

Day 1Day 1Preclinical efficacy Preclinical efficacy

profile profile > to IM> to IM

IC50 < 0.005 µMIC50 < 0.005 µMvsvs

IC50 = 0.02 µMIC50 = 0.02 µM

Phase IIPhase IIAB1010: 7.5 mg/kgAB1010: 7.5 mg/kg

4 centers4 centers

N = 25N = 25(06/05 to 11/06)(06/05 to 11/06)

ASCO 2007ASCO 2007

M6M6

Day 1Day 1

M1M1

PI :PI : A. Le Cesne - VillejuifA. Le Cesne - Villejuif