LUNG CANCER

ASCO 2007

PCI - Overall Survival

PCI

1 year: 27.1% vs. 13.3%

HR: 0.68 (0.52-0.88) p=0.003

Control

(months)

Months from moment of randomization

0

10

20

30

40

50

60

70

80

90

100

0 4 8 16 20 24 28 32 3612

PCI reduces the risk of symptomatic BMet , HR 0.27 p<0.0001

Risk of symptomatic BMet reduced to 15% vs 40% at 1 yr

Slotman et al. ASCO 2007 Abstract #4

Phase III of irinotecan +carboplatin vs. etoposide + carboplatin in ED SCLC

ED SCLCStratification

PS 012, 34

18-70, >70yr

Institution

Carboplatin AUC 4Irinotecan 175 mg/m²day 1 every 3 weeks

Pt no. 105

Carboplatin AUC 4Etoposide 120 mg orally d1-5

every 3 weeks Pt no. 104

MS mos. 1 Yr % CbIr 8.5 34CbE 7.1 24

p=0.02

Hermes et al ASCO 2007 Abstract# 7523

Pre-Op Chemotherapy in Pts with Resectable NSCLC: MRC LU22/NVALT/EORTC 08012

Overall Survival

S CT-S

Events 122 122

5-year OS 45% 44%

HR 1.02

95% CI 0.80, 1.31

p = 0.86

Years from Randomization

Pro

po

rtio

n a

live

and

pro

gre

ssio

n f

ree

0

1.00

0.75

0.50

0.25

CT-S 258:

At risk:

S 261: 39

0

214 167 114 65

31213 160 113 64

51 2 3 4

Nicholson et al. ASCO 2007, Abstract #7518 Gilligan et al Lancet 2007

Concurrent CT/RT +/-consolidation docetaxel

HOG LUN 01-24/USO-023

Toxicity Docetaxel Observation p-value

G 3/4 Infection 11% 0% 0.003

G 3/4 Pneumonitis 9.6% 1.4% <0.001

Hospitalised 28.8% 8.1% <0.001

Treatment Related Death

5.5% 0.0% 0.058

Hanna N, et al. ASCO 2007 Abstract #7512

Bevacizumab 7.5 mg/kg vs. 15 mg/kg AVAiL study

Placebo+ CG

n = 347

Bevacizumab7.5mg/kg + CG

n = 345

Bevacizumab15mg/kg + CG

n = 351

3 months 78.6% 88.5% 80.7%

6 months 52.0% 62.3% 57.5%

9 months 19.2% 28.5% 25.3%

12 months 9.7% 14.1% 14.1%

Median PFS (mos)

6.1 6.7 6.5

Manegold et al. ASCO 2007 Abstract # LBA7514

Randomized Phase III Trial of Gefitinib vs Docetaxel in Japanese Patients

Overall Survival (ITT)Gefitinib Docetaxel

N 245 244

Events 156 150

HR (95.24% CI) = 1.12 (0.89, 1.40) p = 0.330

Median (months) 11.5 14.0

1-year survival (%) 48 54

Supportive Cox analysis with covariates

HR (95% CI) = 1.01 (0.80, 1.27) p = 0.914

Probabilityof Survival

Months0.00

0.25

0.50

0.75

1.00

245 226 197 169 148 127 98 77 63 47 35 29 25 18 9 5 4 1 0Docetaxel:

At Risk:

Gefitinib:

244 233 214 189 173 140 105 87 69 44 35 25 18 14 10 7 6 3 0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

Niho et al. ASCO 2007 Abstract # LBA7509

THE ALGORITHM

ERCC1 mRNA

ERCC 1 Expression

RRM1 Expression

Treatment with Platinum

Carboplatin

+

Docetaxel

High Low

Carboplatin

+

Gemcitabine

RRM1 Expression

Platinum withheld

Gemcitabine

+

Docetaxel

LowHigh

Docetaxel

+

Navelbine

Simon et al ASCO 2007 # 7502

HEAD & NECK CANCER

ASCO 2007

Group ACetuximab 400 mg/m2 initial dose

then 250 mg/m2 weekly + EITHER carboplatin (AUC 5, d1) OR cisplatin (100 mg/m2 IV, d1)+ 5-FU (1000 mg/m2 IV, d1-4):

3-week cycles

Group BEITHER carboplatin (AUC 5, d1) OR cisplatin (100 mg/m2 IV, d1) + 5-FU (1000 mg/m2 IV, d1-4):

3-week cycles

No treatmentCetuximab

Randomized

Progressive disease or unacceptable toxicity

6 chemotherapy cycles maximum

The EXTREME TrialThe EXTREME Trial

Patients at Risk Survival Time [Months]CTX onlyCET + CTX

220 173 127 83 65 47 19 8 1222 184 153 118 82 57 30 15 3

HR (95%CI): 0.797 (0.644, 0.986)Strat. log-rank test: 0.0362

Overall Survival

CTX onlyCET + CTX

Su

rviv

al P

rob

ab

ility

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 3 6 9 12 15 18 21 24

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||| | | |||| ||| ||||| | | || | | || | ||| | | | | ||| | | |

|| | |

10.1 mo7.4 mo

Cetuximab And Weekly Cetuximab And Weekly PaclitaxelPaclitaxel

Eligibility:Eligibility:– KPS KPS 70% 70%– Prior Systemic Chemotherapy Is Only Allowed If Prior Systemic Chemotherapy Is Only Allowed If

Given As Part Of A Multimodal Treatment For Given As Part Of A Multimodal Treatment For Locally Advanced Disease Which Was Completed > Locally Advanced Disease Which Was Completed > 6 Months Prior To Study Entry 6 Months Prior To Study Entry

Dosing Schedule Up To PD/Toxicity:Dosing Schedule Up To PD/Toxicity:– Paclitaxel 80 Mg/M2 IV WeeklyPaclitaxel 80 Mg/M2 IV Weekly– Cetuximab 400/250 Mg/M2 IV WeeklyCetuximab 400/250 Mg/M2 IV Weekly

Response Assessment (RECIST):Response Assessment (RECIST):– CT/MRI Every 6 WeeksCT/MRI Every 6 Weeks

Best Best ResponseResponse

NN %%

CRCR 1010 2424

60% OR60% OR88% DCR88% DCRPRPR 1515 3636

SDSD 1212 2828

PDPD 55 1212

TotalTotal 4242 100100

Cetuximab And Weekly Cetuximab And Weekly PaclitaxelPaclitaxel

Final Results of a Phase II Study of Final Results of a Phase II Study of Erlotinib, Docetaxel and Cisplatin Erlotinib, Docetaxel and Cisplatin

in Patients with in Patients with Recurrent/Metastatic Recurrent/Metastatic

Head and Neck CancerHead and Neck Cancer

EfficacyEfficacyN = 48N = 48

Complete ResponseComplete Response 4 Pts (8%) 4 Pts (8%) Partial Response Partial Response 28 Pts (58%)28 Pts (58%) Stable Disease Stable Disease 13 Pts (25%)13 Pts (25%)

Overall Response Rate Overall Response Rate 66%66%

Disease Control Rate Disease Control Rate 91%91%

Only 3 Pts Progressed After 2 Cycles Of Only 3 Pts Progressed After 2 Cycles Of TreatmentTreatment

Intratumoral EGFR Antisense DNA in Intratumoral EGFR Antisense DNA in Recurrent SCCHN: A Phase I TrialRecurrent SCCHN: A Phase I Trial

Clinical ResponseClinical Response17 Evaluable for Response17 Evaluable for Response

Complete Response Complete Response CRCR 2 2

Partial ResponsePartial Response PRPR 3 3

Stable DiseaseStable Disease SD SD 2 2

Progressive DiseaseProgressive Disease PDPD 10 10

Response Rate:Response Rate: 5/17 (29%)5/17 (29%)

DCR: DCR: 7/17 (41%)7/17 (41%)

Pre-Treatment

Post-Treatment

18

A Phase 2 Study Of Axitinib (AG-A Phase 2 Study Of Axitinib (AG-013736), A Potent Inhibitor Of 013736), A Potent Inhibitor Of

VEGFRs, In Patients With Advanced VEGFRs, In Patients With Advanced Thyroid CancerThyroid Cancer

Target VEGFR-1 VEGFR-2 VEGFR-3Cellular IC50(nM) 0.1* 0.2 0.1 – 0.3

Tight Fit Of Axitinib In The Kinase Tight Fit Of Axitinib In The Kinase Domain Of VEGFR-2Domain Of VEGFR-2

Receptor Protein Surface

Receptor Protein

Backbone

Axitinib

Best Response by Histology*Best Response by Histology*

Histology (n) PR (N=18)SD

(N=25)PD (N=7)

Follicular (15) 7 7 1

Papillary (30) 7 13 2

Medullary (12) 3 4 3

Anaplastic (2) 1 0 1

Other(1) 0 1 0

*Excludes 9 Indeterminate Assessments And 1 Ineligible Patient*Excludes 9 Indeterminate Assessments And 1 Ineligible Patient

A Growing EpidemicA Growing EpidemicA Therapeutic TargetA Therapeutic Target

Human PapillomavirusHuman Papillomavirusand Oropharyngeal Cancer:and Oropharyngeal Cancer:

Oropharynx Cancer and HPV-Oropharynx Cancer and HPV-20072007

Population At RiskPopulation At Risk– Increasing Numbers of Oropharynx CancerIncreasing Numbers of Oropharynx Cancer

» 40-70% Of New Oropharynx Cases are HPV+40-70% Of New Oropharynx Cases are HPV+» Advanced Stage At DiagnosisAdvanced Stage At Diagnosis

– Sexually TransmittedSexually Transmitted» Younger, Less Alcohol, Less Tobacco, Both Younger, Less Alcohol, Less Tobacco, Both

SexesSexes– Preventive Vaccine AvailablePreventive Vaccine Available– Different Prognosis, Different BiologyDifferent Prognosis, Different Biology

» More Responsive To Radiotherapy?, More Responsive To Radiotherapy?, Chemotherapy? Chemotherapy?

GASTRO-INTESTINAL CANCER

ASCO 2007

Perioperative CT in liver metastasesEORTC Intergroup phase III study 40983

Randomize

SurgeryFOLFOX4 FOLFOX4

Surgery

6 cycles (3 months)

N=364 patients

6 cycles(3 months)

Primary endpoint: demonstrate an improvement in progression-free survival with peri-operative FOLFOX4 compared to surgery alone

Secondary endpoints : overall survival, tumor resectability, tumor response, safety

B Nordlinger et al., ASCO 2007, A5 (LBA5)

Progression-free survival in eligible pts EORTC Intergroup phase III study 40983

HR= 0.77; CI: 0.60-1.00, p=0.041

Periop CT

28.1%

36.2%

+8.1%At 3 years

(years)

0 1 2 3 4 5 6

0

10

20

30

40

50

60

70

80

90

100

O N Number of patients at risk :125 171 83 57 37 22 8

115 171 115 74 43 21 5

Surgery only

CRYSTAL study :cetuximab : 1rst line in mCRC !

Phase III : international => 1217 patients

FOLFIRIFOLFIRI

FOLFIRI + Cetuximab (400 mg/m² puis 250 mg/m² hebdo)FOLFIRI + Cetuximab

(400 mg/m² puis 250 mg/m² hebdo)

Primary endpoint : PFS

secondary : OS, Responses , toxicity

E. Van Cutsem, ASCO 2007, Abstract 4000

R

CRYSTAL study :cetuximab : 1rst line in mCRC !

FOLFIRI + Cetuximab FOLFIRI p

n 608 609

Median PFS(months)

8.9 8 0.036

Response rate(%)

46.9 38.7 0.005

Cetuximab added to FOLFIRI significantly increases RR and PFS

OR progression : 0.85

Toxicity idem apart cutaneous rash (19% gr 3-4)

E. Van Cutsem, ASCO 2007, Abstract 4000

…cetuximab : 2d line in mCRC !

EPIC study (1)

Phase III: international ; 1298 pts

C.Eng et al., ASCO 2007, Abstract 4003

mCRC progressing under oxaliplatine

EGFR + in IHC

irinotécan 350 mg/m²/3s

+ cetuximab(400 mg/m² then 250 mg/m² hebdo)

irinotécan 350 mg/m²/3s

+ cetuximab(400 mg/m² then 250 mg/m² hebdo)

irinotécanirinotécan

Main endpoint : Overall Survival

R

… …cetuximab : 2d line in mCRC !EPIC study (2)

No difference in overall survival

Increased PFS (HR 0.69, p<0.0001)

Higher RR: 16.4% vs 4.2%, (p<0.0001)

Better QoL

C.Eng et al., ASCO 2007, Abstract 4003

Cross-over may explain the absence of OS advantage ?

NO 16966 : Oxaliplatin +/- beva in 1rst line CCRM: Non inferiority Xelox vs FOLFOX 4

International Phase III

First part, 634 pts

L. Saltz, J Cassidy, ASCO 2007, Abstract 4030

XELOXXELOX

FOLFOX 4FOLFOX 4

After 2003 : factorial design 2X2, 1400 pts

XELOX +/- Beva idemXELOX +/- Beva idem

FOLFOX 4+/- beva (5mg/kg/2s ou 7.5 mg/kg/3s)

FOLFOX 4+/- beva (5mg/kg/2s ou 7.5 mg/kg/3s)

R

R

Survie

21.319.9

1.0

0.8

0.6

0.4

0.2

00 6 12 18 24 30 36

Mois

Interest of Beva : Beva +CT > Placebo +CT

L. Saltz et al., ASCO 2007, Abstract 238 actualized

PFS estimée

HR = 0.83 [97.5% CI 0.72–0.95] (ITT)

p = 0.0023

9.48.0

1.0

0.8

0.6

0.4

0.2

00 5 10 15 20 25

FOLFOX+placebo/XELOX+placebo N=701;547 évenements

FOLFOX+bevacizumab/XELOX+bevacizumab N=699;513 évènements

Mois

HR = 0.89 [97.5% CI 0.76–1.03]

p = 0.0769

XELOX/FOLFOX+bevacizumabN=699 ; 420 évènements

XELOX/FOLFOX+placebo N=701 ; 455 évènements

SSP SG

166 Patients CCRm +; EGFR +

OMS 0-1 Progressiveunder CPT11

166 Patients CCRm +; EGFR +

OMS 0-1 Progressiveunder CPT11

S. Tejpar et al, ASCO 2007, Abstract 4037

Randomized Phase I/II (multicentric)

Bras B CAMPTO + ERBITUX

Dose escalation: 50 mg/m²/s until 500mg/m²

Bras B CAMPTO + ERBITUX

Dose escalation: 50 mg/m²/s until 500mg/m²

Bras ACAMPTO +ERBITUX

« classic »

Bras ACAMPTO +ERBITUX

« classic »

Bras C non eligibles pts

For randomisation because

Bras C non eligibles pts

For randomisation becauseTox > gr 2cut Tox > gr 1

J22

CAMPTO+ERBITUX21 days

CAMPTO+ERBITUX21 days

EVEREST : final results

R

Bras A Bras B Bras C

n 45 44 68

Response rate confirmed

16 30 25

Median FPS (months) 3.9 4.8 4.7

Median OS (months) 10.0 8.6 8.7

Survival at 18 months 9% 28% 21%

EVEREST : final results

S. Tejpar et al, ASCO 2007, Abstract 4037

Metastatic colorectal cancer: circulating tumoral cells (CTC) are predictive for survival !

N.J. Meropol et al., ASCO 2007, Abstract 4010

N = 456 mCRC L1, L2, L3

7,5 ml blood samples- immunomagnetic separation cytokeratine-PE, CD45-APC, DAPI.=> initial level and during treatment

Changes in CTC status at 3 &t 5 weeks influence overall survival

Cells / 7,5 ml OS(m)

< 3 then < 3 17,7

> 3 then < 3 11,0

> 3 then > 3 3,7

< 3 then > 3 10,9

P = 0.002

P = 0.0002

MOSAIC: Overall Survival: Stage II and Stage III

A. de Gramont et al., ASCO 2007, Abstract 4007 actualisé

Data cut-off: January 2007

FOLFOX4 stage II

LV5FU2 stage II

FOLFOX4 stage III

LV5FU2 stage III

Mois

Pro

bab

ilit

y

1.0

0.8

0.6

0.4

0.2

0

0.9

0.7

0.5

0.3

0.1

0 6 12 18 24 6030 36 42 48 54 66 9672 78 84 90

HR [95% CI]

Stade II 1.00 [0.71–1.42]

Stade III 0.80 [0.66–0.98]

0.1%

4.4%

p=0.996

p=0.029

0.0

surgery

V. Boige et al., ASCO 2007, Abstract 4510 actualized

Logrank p value = 0.0033Hazard Ratio = 0.65 (95% CI 0.48-0.89)

1.00

0.80

0.60

0.40

0.20

Years

00.5

3 4 521 6 7

CT + surgery

PFS

0.0

1.00

0.80

0.60

0.40

0.20

Years

0 3 4 521 6 7

Logrank p value = 0.021Hazard Ratio = 0.69 (95% CI 0.50-0.95)

surgery

CT + surgery

Overall survival

Adenocarcinoma from stomach and low esophagus

FFCD-FNLCC Accord 07 trialNeoadjuvant Chemotherapy vs surgery alone

=> Neoadjuvant FU-P is a new standard in resectable gastric and esophageal adenocarcinoma

=> Confirmation of the MAGIC trial

S1 seul vs S1-cisplatine

in 1srt line Avanced Gastric Cancers: SPIRITS study

H. Narahara et al., ASCO 2007, Abstract 4514 actualisé

S-140 mg/m2 2 fois/j 28j - repos 14 j

S-140 mg/m2 2 fois/j 28j - repos 14 j

Etude phase III

305 ptsnon résécablesou récidivants

L1

Etude phase III

305 ptsnon résécablesou récidivants

L1S-1

40 mg/m2 2 fois/j 21 j - repos 14 j

CDDP60 mg/m2 J8

S-140 mg/m2 2 fois/j 21 j - repos 14 j

CDDP60 mg/m2 J8

Objectif principal = SG

R

S1 seul vs S1-cisplatine

in 1srt line Avanced Gastric Cancers: SPIRITS study

H. Narahara et al., ASCO 2007, Abstract 4514 actualisé

S1 S1 - CDDP P

RR 31,1% 50,4% 0.0018

OS (mois)11 13 0,0366

OS 1 year 46.7% 54.1%

OS: 2 year15.3% 23.6% <0.0001

PFS (mths)4.0 6.0

3/4 Neutrop 10,2% 39,1%

Pancreatic Cancer

Gemcitabine (G) + bevacizumab (B)vs G + placebo (P)

H.L. Kindler et al., ASCO 2007, Abstract 4508

1rst line palliative : phase III (double blind CALGB 80303) (525 advanced pancreatic cancer)

Toxicity grade 3/4

% GB(n = 268)

GP(n = 257)

AHT 8 2

digestive Perforation

0,4 0

Proteinuria 5 1

Réponse

% GB(n = 302)

GP(n = 300)

RC 1 2

PR 10 8

SD 36 31

T Control 47 41

HR=1.00

p=0.99

Bevacizumab 4.9 moPlacebo 4.7 moHR = 1.00P = 0.99

Bevacizumab 5.8 moPlacebo 6.1 moHR = 1.03P = 0.78

0 5 10 15 20 25

Mois

0.0

0.2

0.4

0.6

0.8

1.0

Su

rvie

0 5 10 15 20 25

0.0

0.2

0.4

0.6

0.8

1.0

Mois

Su

rvie

PFS OS

SorafenibMedian: 46.3 weeks(95% CI: 40.9, 57.9)

Su

rviv

al

Pro

bab

ilit

y

Weeks

Hazard ratio (S/P): 0.69 (95% CI: 0.55, 0.88)

P=0.00058*

PlaceboMedian: 34.4 weeks (95% CI: 29.4, 39.4)

1.00

0

0.75

0.50

0.25

0 808 16 24 32 40 48 56 64 72

*O’Brien-Fleming threshold for statistical significance was P=0.0077.

0274 241 205 161 108 67 38 12 0Patients at risk

Sorafenib:0276 224 179 126 78 47 25 7 2Placebo:

299303

Phase III SHARP TrialOverall survival (Intention-to-treat)

GENITOURINARY CANCERS

ASCO 2007

International Kidney Cancer Working Group : Prognostic Factors for Survival1

Group Med. OS Good Risk 27.8 mos Interm Risk 11.4 mos Poor Risk 4.1 mos

Prognostic Factors Risk Groups : Survival

•3748 untreated RCC patients from 11 centers in US and Europe

1 IKCWG, ASCO, 2007

Renal Cell Carcinoma ASCO 2005 to 2007

• A series of phase 3 clinical trials presented which have defined a new treatment approach for renal cell carcinoma

Trial Prior Rx Clear Cell

2005 : TARGETs trial (sorafenib) Yes Yes

2006 : Sunitinib vs IFNα No Yes

Temsirolimus ± IFNα No No

2007 : IFNα ± Bevacizumab No Yes

AVOREN Trial: B017705: study design

Bevacizumab + IFN-α2a (n=327)

IFN-α2a + placebo (n=322)

PD

PD

P.I. Bernard Escudier

RCC patients(n=649)

1:1

Bevacizumab/placebo 10mg/kg i.v. q 2w until progressionIFN-2a 9MIU s.c. three times/week (maximum of 52 weeks) (dose reduction allowed)

HR=0.63, p<0.0001Median progression-free survival:

Bevacizumab + IFN = 10.2 months

Placebo + IFN = 5.4 months

Pro

bab

ility

of

bei

ng

p

rog

ress

ion

-fre

e

Progression-free survival (investigator assessed)

Time (months)0 6 12 18 24

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

05.4 10.2

RCC Treatment Alogrithm : 2007 *

Regimen Setting Therapy Options

Treatment Naïve Patient

MSK Risk : Good or Intermediate

MSK Risk : Poor

Treatment Refractory Patient (≥ 2nd Line)

Cytokine Refractory

Refractory to VEGF/VEGFR or mTOR Inhibitors

Sunitinib? Bevacizumab ± IFNα

HD IL-2

? Sorafenib

Temsirolimus Sunitinib

?Sorafenib

Sorafenib Sunitinib

?Investigational ?Sequential TKI’s or VEGF Inhibitor

*Adapted from M Atkins, ASCO 2006

T4bN0M0 or

TxN2-3 or M1

TCC of Urothelium

No prior Chemo

RANDOMIZE

Gemcitabine 1000 mg/m2 days 1, 8 & 15Cisplatin 70 mg/m2 day 2

Paclitaxel 80mg/ m2 on days 1 and 8

Cisplatin 70 mg/m2 on day 1

Gemcitabine 1000 mg/m2 on days 1 and 8

Arm 1 is given as a 4 week cycle (28 days)

Every 21 days if d15 is withheld or missed

Arm 2 is given as a 3 week cycle (21 days)

Opened in May 2001. Closed in June 2004

EORTC/Intergroup Study 30987

(years)

0 1 2 3 4 5 6

0

10

20

30

40

50

60

70

80

90

100

O N Number of patients at risk : Treatment247 315 159 76 34 7 0

239 312 185 86 35 13 2

Gem+Cis

Gem+Cis+Pac

Overall Duration of Survival

Overall Logrank test: p=0.100

Overall Survival

Gem/Cis 247/315 12.8 mo 1

Pac/Cis/Gem 239/312 15.7 mo 0.86 (0.72-1.03) 0.10

14% improvement (n.s.)

Sternberg et al (abst. 5019): Satraplatin vs. Prednisone

• SPARC trial – Satraplatin, oral platinum compound

• Regimen: (patients failed prior chemotherapy)– Satraplatin 80 mg/m2/day x 5 q 5 weeks + Prednisone

– Placebo + Prednisone

• 950 patients, 9/2004 – 1/2006

• Satraplatin wins?– PSA response: 25% vs. 12%

– Pain response 24% vs. 14%

– Progression-free survival p< 0.00000003

– Time to pain progression

• OVERALL SURVIVAL???????

SPARC: Progression Free Survival

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60 70 80 90

Weeks

Surv

ival

Pro

babi

lity

(%)

No. at Risk

HR: 0.67 (95% CI: 0.54 - 0.83)

P = 0.0006

Satraplatin + Prednisone

Placebo + Prednisone

327

160

107 28

39 8

19 1

9S

P

167 69 28 13 5

61 16 4 1

S+P P

Median (wks) 10.1 9.1

GYNECOLOGIC CANCER

ASCO 2007

# 5503 RT +/- Chemotherapy Early-stage HR Endometrial Ca

• 382 pts

• Stage I,II,IIIA (peritoneal cytology only)

• External beam RT

• Chemo: Initially 4 courses cisplatin/doxorubicin; modified to permit carboplatin-based regimen

• Compliance: RT 93%; Chemo 75%

• Median follow-up 4.3 years

#5503

• Progression-free survival Hazard ratio 0.62 (p= 0.03) Absolute difference at 5-years: 7% (79% versus 72%)

• Cancer specific overall survival Absolute difference at 5-years: 5%

• in favor of combined modality regimen

• Investigators question: “Role of RT?”

# 5504 Adjuvant RT after Surgery High Risk Stage I Endometrial Ca

• RT vs observation until relapse

• Vaginal brachytherapy permitted in all patients (50% of women in trial)

• 906 pts; well-balanced prognostic factors

• 90% pts received protocol therapy

• Overall morbidity (including surgery): Observation arm: 26%; RT arm: 60%

#5504

• No difference in recurrence-free; disease-specific or overall survival (hazard ratio 1.01; p= 0.98)

• Vaginal brachytherapy (non-randomized analysis) reduced risk isolated vaginal recurrence HR 0.53; p=0.038

• Data raise question of role of routine adjuvant external beam radiation therapy in high-risk early stage endometrial cancer

#5505 “After 6 protocol”

• Observation vs single agent paclitaxel (175 mg/m2 every 3-weeks x 6 cycles)

• 200 pts

• Clinical complete response (48%)

• Pathological complete response (52%)

• No difference in progression-free or overall survival between study arms

# 5506 Gemcitabine versus LD 2nd-line Therapy Ovarian Cancer

• Gemcitabine (1000 mg/m2 over 30 minutes day 1, 8, 15 q-4 week schedule)

• Liposomal doxorubicin (40 mg/m2 q-4 weeks)

• Eligibility: Platinum-resistance and recurrence (up to 12 months)

• No difference in progression-free and overall survival