lung cancer asco 2007. pci - overall survival pci 1 year: 27.1% vs. 13.3% hr: 0.68 (0.52-0.88)...
TRANSCRIPT
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
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?
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%
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)
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
# 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