Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as...
-
Upload
margery-austin -
Category
Documents
-
view
223 -
download
0
Transcript of Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as...
![Page 1: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/1.jpg)
Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage III-IV Melanoma
DH Lawson, SJ Lee, AA Tarhini, KA Margolin, MS Ernstoff, JM KirkwoodWinship Cancer Institute of Emory University, Dana-Farber Cancer Institute, University of Pittsburgh Cancer Institute, University of Washington, Dartmouth Hitchcock Medical Center
![Page 2: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/2.jpg)
Objectives
• Primary objective:– To compare OS of patients given GM-CSF vs
placebo• Secondary objectives
– To compare DFS of patients with GM-CSF vs placebo
– To compare DFS of HLA-A2+ patients given peptide vaccine vs. placebo
– To compare OS of HLA-A2+ patients given peptide vaccine vs. placebo
![Page 3: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/3.jpg)
GM-CSF+ Peptide Vaccine
Placebo+ Peptide Vaccine
GM-CSF+ Peptide Placebo
Placebo+ Peptide PlaceboRA
ND
OM
IZE
GM-CSF
GM-CSF Placebo
RA
ND
OM
IZE
HLA-A2Positive
HLA-A2Negative
Stratify:
HLA-A2 Status
1. Positive 2. Negative
Site of Metastases
1. Visceral 2. Non-visceral 3. Visceral/Non-visceral
Number of Metastases
1. 1 2. 2 - 3 3. 4 or more
![Page 4: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/4.jpg)
Eligibility for E4697: Stage III• Intransit metastases including local recurrence
• Gross extracapsular extension
• Recurrence in previously resected nodal basin
• Four or more involved nodes
• Ulcerated primary with any clinically involved nodes
• Locoregional recurrence after IFN or S0008
![Page 5: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/5.jpg)
Eligibility for E4697
• Resected locoregional mucosal melanoma
• Completely resected stage IV melanoma,– Cutaneous, mucosal, ocular, and unknown
1º
![Page 6: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/6.jpg)
Treatment Plan
• GM-CSF 250 mcg SC 14 days of 28 for one year (13 cycles)
• Patients with resectable recurrences encouraged to continue 6 months past recurrence or for one year, whichever is longer
• Disease assessments every 3 mos
•
![Page 7: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/7.jpg)
Treatment Plan
• Vaccinations on days 1 and 15 of first cycle, then day 1 of subsequent cycles.
• Peptides used:–Tyrosinase: 368-376 (370D)–gp-100: 209-217 (210M)–MART-1: 27-35
![Page 8: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/8.jpg)
Statistical Considerations• 800 patients gives 80% power to
detect a 33% increase in median survival from 40 to 53 months with 2-sided type 1 error rate of 0.05
• 80% power to detect 24% increase in DFS from 11 to 13.6 months
• Placebo controlled to enhance validity of the DFS endpoint
![Page 9: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/9.jpg)
E4697: Accrual
• 815 pts accrued between December 29, 1999 and October 31, 2006 – 53.5% HLA-A2+– 46.5% HLA-A2-
• 72 ineligible• 743 included in this analysis
– 368 received GMCSF– 375 received GMCSF-placebo
![Page 10: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/10.jpg)
Data Analyses
Unblinding specified in protocol at 30 months from completion of treatment of the last patient (April, 2009) even if full information not reached by then.
![Page 11: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/11.jpg)
Data Analyses
September 2009 analysisPositive effect of GM-CSF on DFS (p=.03) with Hazard Ratio (HR) 0.82, 95% CI(.69, .98)
No significant effect on OS (p=.55) with HR 0.94, 95% CI (.75, 1.16)
![Page 12: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/12.jpg)
Data Analyses
Updated analysis for ASCO planned
for April 2010
![Page 13: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/13.jpg)
Current Status
• 345 deaths
• 86% information time
• Full information anticipated in 2014
• Results of April, 2010 analysis presented today
![Page 14: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/14.jpg)
DFS by GM-CSF (n=743)
P = 0.14
HR = 0.88, 95% CI(.73,1.04)
Median DFS•Placebo: 9.2 mos, 95% CI (7.68, 12.48)•GM-CSF:11.5 mos, 95% CI (9.72, 15.48)
![Page 15: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/15.jpg)
OS by GM-CSF Treatment Status
P= 0.78HR= 0.96, 95% CI(.78,1.04)
Median OS:• Placebo : 62.4 mos, 95% CI (45.6, -)• GM-CSF: 69.6 mos, 95% CI (50.4, -)
![Page 16: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/16.jpg)
Effect of Peptide Vaccination on Disease Free and Overall Survival in HLA-A2+ Patients
![Page 17: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/17.jpg)
DFS by PEP in HLA-A2+ (n=398)
P=.709HR=.93, 95%CI(.73,1.27)
![Page 18: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/18.jpg)
OS by PEP in HLA-A2+ (n=398)
P =.670HR=.94, 95%CI(.70,1.26)
![Page 19: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/19.jpg)
Subset Analysis of Effect of GMCSF on OS and DFS by Stage
• Stage IIIB and IIIC: 374 pts• Stage IV: 258 pts
![Page 20: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/20.jpg)
Stage III Melanoma
p = 0.52HR=.92, 95%CI(.72,1.17)
DFS OS
p = 0.80HR=.97, 95%CI(.71,1.31)
![Page 21: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/21.jpg)
Stage IV MelanomaDFS OS
P= 0.04HR=.74, 95%CI(.56,.99)
P= 0.07HR=.72, 95%CI(.50,1.02)
![Page 22: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/22.jpg)
Conclusions
• Neither GMCSF nor peptide vaccination achieved OS and DFS objectives
• There is a suggestion of favorable effect of GMCSF on DFS
• Subset analysis suggests effects of GMCSF on DFS and OS are largest among Stage IV subjects
![Page 23: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/23.jpg)
Conclusions
• Further study of adjuvant GMCSF is warranted (patients, dose, duration)
• Use of GMCSF in the adjuvant setting is worthy of discussion (IFN failures, resected stage IV)
• Laboratory immunologic responses in relation to clinical outcome are under investigation
![Page 24: Abstract 8504: E4697: Phase III Cooperative Group Study of Yeast Derived GM-CSF vs Placebo as Adjuvant Treatment of Patients with Completely Resected Stage.](https://reader036.fdocuments.in/reader036/viewer/2022081514/56649ea85503460f94bab5fc/html5/thumbnails/24.jpg)
Acknowledgements
• Coordinating Centers of ECOG, SWOG, and CALGB
• PI’s, Research Nurses and Coordinators at the sites
• Carol Hill, RN, PIN nurse• As always, our patients and their
families