adjuvant chemotherapy for colorectal cancer
DESCRIPTION
Adjuvant Chemotherapy for Colorectal Cancer. Ronald L. Burkes, M.D. Historic Synopsis in the Treatment of Colorectal Cancer. 5-FU has anti-tumor activity 1958 Biochemical modulation of 5-FU with LV 1989 HAI with FUDR RR 1993 Responses seen post bolus 5-FU with - PowerPoint PPT PresentationTRANSCRIPT
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Adjuvant Chemotherapy
for Colorectal Cancer
Ronald L. Burkes, M.D.
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Historic Synopsis in the Treatment of Colorectal Cancer
• 5-FU has anti-tumor activity 1958
• Biochemical modulation of 5-FU with LV 1989
• HAI with FUDR RR 1993• Responses seen post bolus 5-FU with infusional 5-FU 1993• Adjuvant CT (5-FU/Lev or 5-FU/LV) for colon cancer 1994
• Adjuvant CT + RT for rectal cancer 1995
• New drugs - CPT-11/Tomudex/Oxaliplatin 1993-2002• MTD – Cetuximab; Bevacizumab; 2000-2011
Panitumumab
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Adjuvant Therapy for
Stage II Colon Cancer:
Yes, No and Maybe So
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Why is the Situation in Stage II Colon Cancer Less Clear than Stage III
DFS and survival difference is small – relatively low activity of adjuvant treatment
High patient numbers required to show a difference
Stage II is a heterogeneous disease for
Clinical factors
Pathological factors
Molecular factorsMost trials were not stratified for these factors
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Why is Adjuvant Therapy Effective in Stage III but not Stage II Disease:
The Numbers
To detect a 2% survival difference between Rx and controls (90% power with significance level of .05) would require a sample size of 9680 pts per group
To detect an absolute risk reduction of 2.5% at 3 yrs and 4% at 5 (85% & 75% survival) would require a study of 8000 and 4700 pts respectively
Benson JCO 22:3408, 2004
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Stage II Colon Cancer: Poor Prognostic factors
• Inadequate staging
• Clinical/pathological features
• Molecular/enzymatic factors
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Poor Prognostic Factors: Inadequate Staging
• Variability of the number of lymph nodes sampled
• Rreports have independently recommended that >10 lymph nodes (ideally >12) be examined to classify a colon cancer as truly N0Intergroup adjuvant trialNational Cancer Data Base
JCO, 2003Ann Surg Oncology, 2003
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Clinical/Pathological Features: Subset Analysis for B2 Intergroup Study
(7 year survival)
Covariate Observation 5-FU/Lev
Adhesion 70% 82%
Invasion 64% 86%
Obstruction 58% 70%
Perforation 51% 67%
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Stage II a Heterogeneous Disease: Molecular Factors
• Microsatellite instability – MSI-Hi > MSS (stg for stg)
• MSI-H vs MSS with CT – ND
• MSS with CT - ↑ survival
• MSI-H with CT – ND (trend to survival)
• 18q LOH – NO!
• DNA ploidy
• EGFR+
• P53
• Microarray gene expression profiling
• ???KRAS
Gryfe NEJM 342:69, 2000Ribic NEJM 349:247, 2003Watanabe NEJM 344:1196, 2001Barrier JCO 24:4685, 2006
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Other Prognostic Pathological Variables
• Grade
• Lymphovascular invasion
• Perineural invasion
• ?Immune response – lymphocytic infiltrate confers a better prognosis; fibrosis a worse prognosis
• ? Tumour budding
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Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III
Colon Cancer
• 3 factors predict prognosis
- nodal status – N0 vs N1-4 vs >5
- depth of invasion – T1/2 vs T3 vs T4
- grade – low vs high
• www.mayoclinic.com/calcs
• Stage II - 17% relative reduction in risk of recurrence (4% ↑ in 5 yr DFS; 72% vs 76% but overall survival was 80% vs 81%)
Gill JCO 22:1797, 2004
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Adjuvant on Line
• Depth of invasion• Histologic grade• # of nodes involved• # of nodes examined• Derived tumor stage• Age• General health (# of comorbid conditions)• Treatment
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5-FU + Levamisole for Stage II/Dukes’ B2 Colon
Cancer Obs 5-FU/Lev
n 159 159
RFS (7 yr) 71% 79% p=.1
OS (7 yr) 72% 72% p=.83
recurrence by 31% (p=.1)• disparity secondary to: - higher rates of non-colon ca deaths with CT - salvage surgery
Moertel JCO 13: 2936, 1995
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IMPACT B2 Adjuvant Trials (n=1016)(GIVI0, NCIC, FFCD, NCCTG, Siena)
Pooled Analysis
5-FU/FA Control (370/200)
EFS (5 yrs) 76% 73%
OS (5 yrs) 82% 80%
JCO 17:1356, 1999 (Lancet 345:939,1995)
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NSABP Colon Trials5 Year Survival
C-01 MOF OP
C-02 PVI OP
C-03 FU-LV MOF
C-04 FU-LV FU-LEV
• All Patients 67 60 74 67 76 66 75 70
• Dukes B 75 72 88 76 92 84 85 81
• Dukes C 59 50 58 56 70 59 67 63
Benefit for stage II same or greater as for stage III
mortality, recurrence or DFS event rate from CT irrespective of stage
30% less mortality for Dukes’ B 18% less mortality for Dukes’ C
Mamounas JCO 17: 1349,1999
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Cancer Care Ontario Practice Guidelines for Stage II Colon Cancer
August, 1997• 31 RCT’s• 3 meta-analysis• 1 evidence-based consensus
statement
Update: April, 2000• 4 meta-analysis• New or updated reports on 19 RCT’s
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Cancer Care Ontario Practice Guidelines for Stage II Colon Cancer
• Adjuvant therapy is not recommended
• Patients with high risk factors have a poorer prognosis and adjuvant CT could be considered
- bowel obstruction
- tumor adhesion
- invasion
- perforation
- aneuploidyFigueredo Ca Prev Control 1: 379, 1997
CCOPGI: Full Report – April, 2000
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Systematic Review from the CCO Program in Evidence-Based Care’s GI
Disease Site Group: Conclusions
• No compelling evidence to use systemic adjuvant therapy.
• There probably is a small benefit that present trials have yet to detect as significant.
• Additional investigation of newer therapies and more mature data from the available trials should be pursued.
Figueredo JCO 22:3395, 2004
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CCO Guidelines as of April, 2008
Routine use of adjuvant chemotherapy for all pts is not recommended
High-risk pts who should be considered for adjuvant therapy include – inadequately sampled nodes, T4 lesions, perforation or poorly differentiated histology
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Conclusions Regarding Adjuvant Therapy: ASCO Guidelines
• Adjuvant therapy for low-risk stage II colon cancer is not supported by randomized controlled trials.
• Adjuvant therapy for hi-risk stage II disease is recommended - ? regimen.
MSI status important
Benson JCO 22:3408, 2005
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FULV vs FLOX for Stage II or III Colon Cancer: NSABP C-07
Wolmark PASCO 23&26: 246s/179s (3500/4005), 2005/2008
FULV FLOX 1209 1200
N0 28.8% 28.9%N1-3 45.7% 44.8%N>3 25.3% 25.6%Neuro - all gr - 85% (29% @ 1 yr) - gr 3 - 8% (.5% @ 1 yr) Oxali dose - 765 mg/m2
(1020 in MOSAIC)
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FULV vs FLOX for Stage II or III Colon Cancer: NSABP C-07
Wolmark PASCO 26:179s (4005)2008
FULV FLOX
DFS - 3 yr
- 5 yr
71.5%
64.2%
76.1%
69.4%
OS - 5 yr
- 6 yr
78.3%
73.5%
80.3% (p=.06)
77.7% (HR=.85)
Surv after recur
22.2 mo 17.6 mo
Global test for interaction between stage and Rx was not significant (p = .7)
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Adjuvant Oxaliplatin + 5-FU + Leucovorin: MOSAIC Trial
Andre NEJM 350:2343, 2004; de Gramont PASCO 23:246 (3501), 2005 and PASCO 25:#4007, 2007
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Adjuvant Oxaliplatin + 5-FU + Leucovorin: MOSAIC Trial
Andre NEJM 350:2343, 2004; deGramont PASCO 23:246 (3501), 2005
LV5FU2 FOLFOX4
1123 1123
Stage II/III 40%/60% 40%/60%
Mean # cycles 11.3 10.7
DI - 5-FU 97.7% 84.4%
- Oxali - 80.5%
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MOSAIC Trial: 5 Year DFSde Gramont PASCO 25:#4007, 2007
LVFU2 FOLFOX4
All pts 67.4% 73.3%
Stage III 58.9% 66.4%
Stage II 79.9% 83.7%
Hi-risk stage II
(576)
74.9% 82.1%
Low-risk stage II
(323)
86.3% 89.1%
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MOSAIC Trial: 6 Year Survivalde Gramont PASCO 25:#4007, 2007
LV5FU2 FOLFOX4
All pts 76% 78.6%
HR = .85; p = .057
Stage III 68.6% 73%
HR = .8; p = .029
Stage II 86.8% 86.9%
HR = 1; p = .996
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MOSAIC Trial: Conclusions
• DFS benefit seen at 3 yrs is maintained at 5 yrs
• At 6 years there is no survival benefit for stage II pts
• Despite a DFS benefit with F4 for hi-risk stage II pts this did not translate into a survival benefit
• There was no increase in 2nd cancers
• There is continued recovery in peripheral neuropathy but 15% of pts still had residual PN at 4yrs (.7% gr 3; 2.8% gr 2; 12% gr 1)
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DFS (3 yr) vs OS (5 yr) as a Primary Endpoint
for Adjuvant Therapy for CRCSargent PASCO 23:249s (3512), 2005/JCO 23:8564, 2005
• 43 Rx arms; n = 20,898 pts• M:F = 54:46• Stg II:III = 34:66• 74% of recurrences in 1st 3 yrs 3 yr DFS & 5 yr OS – cc = .92 for stg III but
only .65 for stg II• DFS excellent predictor of OS at 5 yrs (stg III)• ODAC voted 15 to 0 to accept as a surrogate
marker (Pazdur)
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Microsatellites
• Short, tandemly repeated DNA sequences
• Detected at the molecular level using genomic DNA from either fresh or paraffin-fixed CRC tissues
• Insertion or deletions of nucleotides within repeated sequences of DNA = Microsatellite Instability
• Frequent alterations in DNA sequence length = MSI-H
• MSI is due to defective mismatch repair genes
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dMMR as a Predictive Marker for Lack of Benefit from 5-FU based Adjuvant Chemotherapy
Sargent PASCO 26:180s (#4008), 2008
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MSI-H in Stage II and III Colon Cancer: PETACC 3
Tejpar PASCO 27: #4001, 2009
Stage RFS (HR/p) OS (HR/p)
II & III .56/.018 .548/.006
II .265/.0044 .155/.011
III .693/.06 .699/.12
5-FU (II)
N=625
.228 .18
FOLFIRI
N=608
.296 .143
Prognostic effect of MSI in stage II remained significant even in pts treated with 5-FU
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MSI-H vs MSS Treated With 5-FU: 5 yr DFSSargent vs PETACC 3
Study MSI-H MSS HR/p
Sargent (512)
70% 67% .79/.3
PETACC 3 (625)
83% 66% .5/.0077
Sargent PASCO 26: #4008, 2008Tejpar PASCO 27: #4001, 2009
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Effect of MSI and Treatment With 5-FU: Sargent vs PETACC 3
Sargent PASCO 26: #4008, 2008Tejpar PASCO 27: #4001, 2009
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CRC.3 in Canada
- closed
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Summary of Adjuvant Therapy for
Stage II Colon Cancer: DFS
Moertel IMPACT Gray Mosaic
7 yr 5 yr 5 yr 6 yrObs CT Obs CT Obs CT LV5FU2 F4
71% 79% 73% 76% 73.8% 77.8% 86.8% 86.9%
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Conclusions: Stage II • Prospective clinical trials and meta-analyses have
not yet shown a benefit for adjuvant chemotherapy.
• Present guidelines have recommended against the use of such treatment in “standard risk” patients.
• The use of adjuvant therapy in subsets of stage II pts with ominous clinical, pathological or molecular characteristics appears reasonable although the value of this strategy has not been prospectively validated and the regimen to use is controversial.
• Should patients with MSI-H tumors even receive adjuvant chemotherapy
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Stage III Disease
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Intergroup Trial of Levamisole/5-FU for Stage III Colon Carcinoma
(F/U > 5 yrs, med 6.5)
Obs. Lev. Lev/5-FU
n 315 310 304
Recurrence 177 172 119 p<.0001
Deaths 168 158 121 p=.0007
• decrease recurrence by 40% • decrease death rate by 33%
Moertel Ann Int Med 122: 321, 1995
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IMPACT Trial: Adjuvant 5-FU/FA(GIVI0, NCIC, FFCD)
5-FU/FA (370/200)
Control
736 757
Dukes’ B – 56% 56.8% 55.9%
Dukes’ C – 44% 43.2% 45.1%
EFS (3 yrs) 71% 62% p<.0001
OS (3 yrs) 83% 78% p=.029
Dukes’ B–EFS/OS (%) 79/88 76/90
Dukes’ C-EFS/OS (%) 62/76 44/64
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IMPACT Trial: Adjuvant 5-FU/FA(GIVI0, NCIC, FFCD) - cont’d.
decrease recurrence by 33%decrease mortality by 22%borderline EFS & none for OS
for Dukes’ B
Lancet 345: 939, 1995
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5-FU/LV vs FU/Lev vs 5-FU/LV/Lev: Low dose vs Hi-dose and
6 months vs 12 months
6 months of 5-FU + Leucovorin (LD/HD) became the standard
adjuvant treatment
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Capecitabine vs Mayo in Stage III CRC: X-ACT StudyTwelves NEJM 352: 2696, 2005; GI ASCO #274, 2008
Cape Mayo1004 983
T1/2 10% 10% T3 76% 76% T4 14% 14%
3 yr - DFS 60.8% 56.7% - RFS 65.5% 61.9% - OS 71.4% 68.4%
Toxicity - H/F ↑ - Diarrhea ↓
- Stomatitis ↓ - Neutr ↓
Conclusions:• ↑ RFS• Trend to ↑ DFS & OS benefit• ↑ safety
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X-ACT Trial: Survival Data
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UFT vs FULV (Roswell) in Stage II & III CRC: NSABP CO6
Wolmark PASCO 23:#3508, 2004
Roswell UFT 777 784
II 46% 47%III 54% 54%N1 38% 37%N2 16% 16%RFS 76.4% 74.5%DFS 68.3% 66.9%OS 78.7% 78.7%Diarrhea 28% 29%QOL NDSx distress ↓
Conclusion• Equitoxic• Equivalent• UFT not available in N.A.
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Adjuvant Oxaliplatin + 5-FU + Leucovorin: MOSAIC Trial
Andre NEJM 350:2343, 2004; de Gramont PASCO 23:246 (3501), 2005 and PASCO 25:#4007, 2007
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Adjuvant Oxaliplatin + 5-FU + Leucovorin: MOSAIC Trial
Andre NEJM 350:2343, 2004; deGramont PASCO 23:246 (3501), 2005
LV5FU2 FOLFOX4
1123 1123
Stage II/III 40%/60% 40%/60%
Mean # cycles 11.3 10.7
DI - 5-FU 97.7% 84.4%
- Oxali - 80.5%
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MOSAIC Trial: 5 Year DFSde Gramont PASCO 25:#4007, 2007
LVFU2 FOLFOX4
All pts 67.4% 73.3%
Stage III 58.9% 66.4%
Stage II 79.9% 83.7%
Hi-risk stage II
(576)
74.9% 82.1%
Low-risk stage II
(323)
86.3% 89.1%
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MOSAIC Trial: 6 Year Survivalde Gramont PASCO 25/26:#4007, 2007/08
LV5FU2 FOLFOX4
All pts 76% 78.6%
HR = .85; p = .057
Stage III 68.6% 73%
HR = .8; p = .029
Stage II 86.8% 86.9%
HR = 1; p = .996
Alive with Recurrence
7.8% 6.1%
Time from Recur to Death
24 mo 21 mo
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MOSAIC Trial: Conclusions
• DFS benefit seen at 3 yrs is maintained at 5 yrs
• There is a 6 yr OS benefit for stage III pts
• There was no increase in 2nd cancers
• There is continued recovery in peripheral neuropathy but 15% of pts still had residual PN at 4yrs (.7% gr 3; 2.8% gr 2; 12% gr 1)
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FULV vs FLOX for Stage II or III Colon Cancer: NSABP C-07
Wolmark PASCO 26:179s (4005)2008
FULV FLOX
DFS - 3 yr
- 5 yr
71.5%
64.2%
76.1%
69.4%
OS - 5 yr
- 6 yr
78.3%
73.5%
80.3%
77.7%
Surv after recur
22.2 mo 17.6 mo
Global test for interaction between stage and Rx was not significant (p = .7)
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MOSAIC vs CO.7: 5 year Survival: Stages II/III
Study DFS ∆ HR
MOSAIC 81.3% 2.2% .85
CO.7 80.3% 2.0% .85
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Comparison of Adjuvant Trials
Moertel IMPACT X-ACT MOSAIC
Regimen Lev/5-FU LV/5-FU Cape FOLFOX
DFS (3yr) 63% 62% 64.2% 72.2%
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Role for Adjuvant Irinotecan
• Adjuvant FL (Roswell) vs IFL in Stage III CRC: CALGB 89803 (CO.15)
• FOLFIRI vs LV5FU2 in Stage III Colon Cancer: PETACC 3
• Adjuvant LV5FU2 vs FOLFIRI for Stage III (hi-risk) Colon Cancer: ACCORD-2
All negative studies – no role for adjuvant irinotecan
Saltz PASCO 23: 246 (3500), 2004van Cutsem PASCO 23:3 (8), 2005Ychou PASCO 23: 246s (3502), 2005
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DFS (3 yr) vs OS (5 yr) as a Primary Endpoint for
Adjuvant Therapy for CRCSargent PASCO 23:249s (3512), 2005
• 43 Rx arms; n = 20,898 pts• M:F = 54:46• Stg II:III = 34:66• 74% of recurrences in 1st 3 yrs 3 yr DFS & 5 yr OS – cc = .92 for stg III but
only .65 for stg II DFS excellent predictor of OS at 5 yrs (stg III)• ODAC voted 15 to 0 to accept as a surrogate
marker (Pazdur)
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2 Year DFS in Stage III Colon Cancer: ACCENT (n=12,676 – MOSAIC, X-ACT,
PETACC 3, NSABP CO6/7, C89803)Sargent PASCO 27: #4011, 2009
6 yr5 yr
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2 Year DFS Correlates With 5 & 6 Year OS
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Time-Dependent Patterns of Failure and Treatment Benefit from Adjuvant Therapy for Resectable Colon
Cancer: Lessons from the 20,800-pt ACCENT databaseSargent PASCO 25:#4008, 2007
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ACCENT: Conclusions
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NSABP CO8: FOLFOX +/- BevacizumabWolmark PASCO 27:6s (LBA4), 2009
FOLFOX 6
1338
FOLFOX6+Bev
1334
Stage II 24.9% 24.9%
Stage III (1-3) 45.4% 45.5%
Stage III (4+) 29.7% 29.6%
Hypertension 1.8% 12%
Pain 6.3% 11.1%
Proteinuria .8% 2.7%
Wound compl .3% 1.7%
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NSABP CO8: 3 Year DFS
FOLFOX 6
1338
FOLFOX6+Bev
1334
HR/p
All pts 75.5% 77.4% .89/.15
Stage II 84.7% 87.4% .82/.35
Stage III 72.4% 74.2% .9/.25
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Results: CO8
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Cumulative HRs Over Time: CO-8
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CO-8: What Happens after 1 Year?
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Is Stage Important?
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Allegra PASCO, 2011
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Allegra PASCO, 2011
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Allegra PASCO, 2011
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De Grammont, GI ASCO, 2011
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CRC.2 (N0147)
Stage III FOLFOX6 x 12 + Cetuximab
Issues – KRAS WT only; age < 70; tissue has to be sent to Mayo Clinic by day 42
Trial stopped early
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NO16968: XELOXAAdjuvant Treatment with
Capecitabine and Oxaliplatin (XELOX) in Stage III Colon Cancer
ESMO/ECCO Presidential Session III
D. Haller, J. Tabernero, J. Maroun, F. de Braud, T. Price, E. Van Cutsem, M. Hill, F. Gilberg, K. Rittweger,
H.-J. Schmoll
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Chemo/radiotherapy-naive
stage III colon ≤8 weeks since resection
N=1886
• Primary endpoint: superiority of DFS
• Secondary endpoints: RFS, OS, tolerability
n=944
n=942
RANDO MISATION
Adjuvant XELOX vs 5-FU/LV: NO16968 (XELOXA) Phase III trial
Bolus 5-FU/LV (6 months) Mayo Clinic [n=664]
orRoswell Park [n=278]
XELOX (6 months) capecitabine 1000mg/m2 bid d1–14
oxaliplatin130mg/m2 d1 q3w
8 cycles
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Primary endpoint met:superior DFS with XELOX
HR=0.80 (95% CI: 0.69–0.93)p=0.0045
ITT population
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
Years
XELOX 5-FU/LV
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5-year DFS:benefit with XELOX maintained and increased over time
XELOX 5-FU/LV 1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
Years
ITT population
Δ at 4 years: 6.1% Δ at 5 years: 6.3%
Δ at 3 years: 4.5%
70.9% 68.4%
3-yearDFS
66.5% 62.3%
4-yearDFS
5-yearDFS
59.8%66.1%
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5-year DFS:benefit with XELOX maintained and increased over time
XELOX 5-FU/LV 1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
Years
ITT population
Δ at 4 years: 6.1% Δ at 5 years: 6.3%
Δ at 3 years: 4.5%
70.9% 68.4%
3-yearDFS
66.5% 62.3%
4-yearDFS
5-yearDFS
59.8%66.1%
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Superior RFS with XELOX(excludes all non-cancer-related mortality)
ITT population
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
XELOX 5-FU/LV
72.1% 69.7%
3-yearRFS
67.5% 63.3%
4-yearRFS
5-yearRFS
60.9%67.8%
HR=0.78 (95% CI: 0.67–0.92)p=0.0024
Δ at 4 years: 6.4% Δ at 5 years: 6.9%
Δ at 3 years: 4.6%
Years
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Trend to improved OS with XELOX
ITT population
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
XELOX 5-FU/LV
Δ at 5 years: 3.4%
HR=0.87 (95% CI: 0.72–1.05)p=0.1486
Years
77.6%
5-yearOS
74.2%
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Years
2 4 6
0.4
0.6
0.8
1.0
0
0.4
0.6
0.8
1.0
Years
1. André et al. JCO 2009
8 2 4 60 8
Cross-trial comparison of MOSAICand XELOXA: OS in stage III disease
XELOX
5-FU/LV
FOLFOX4
LV5FU2
XELOXA(57 mo) MOSAIC1
(81.9 mo)
ITT population
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1.0
0.6
0.8
1. André et al. JCO 2009
1 2 3 4 5 6 7 8
Cross-trial comparison of MOSAICand XELOXA: OS in stage III disease
Years
XELOX (n=944)
FOLFOX4 (n=672) –
5-yr OS 6-yr OS
72.9%
77.6%
NO16968 (XELOXA)*
MOSAIC1**
–
*Median observation time: 57.0 months**Median follow-up: 81.9 monthsITT population
0.4
0
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*Values <1 favor oxaliplatin-based therapy vs. 5-FU/LV.†Data for oxaliplatin-based regimens.
Hazard ratio (95% CIs)*DFS OS
ACCENT analysis1†
<70 years, n=3877 0.77 (0.68,0.86) 0.81 (0.71,0.93)
≥70 years, n=703 1.04 (0.80,1.35) 1.19 (0.90,1.57)
XELOXA2
<70 years, n=1477 0.79 (0.66,0.94) 0.86 (0.69,1.08)
≥70 years, n=409 0.87 (0.63,1.18) 0.94 (0.66,1.34)
XELOXA and ACCENT: Comparing DFS and OS by Age
MOSAIC showed no benefit for patients >65
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X-ACT Trial and the Affect of Age: 5 yr DFSTwelves World Congress on G.I. Cancer, June 2010
Age N Cape 5-FU Interactive p-value
>70 1589 59% 54% NS
<70 396 58.8% 55.8% NS
Supports capecitabine in pts >70
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Extended survival after recurrence ’s the DFS and OS relationship
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How to Follow Patients Post Adjuvant Therapy
Examine and do BW including CEA every 3 months (pre-op CEA)
CT chest, abdomen and pelvis every 6 months x 3 years and then annually x 2 years
Colonoscopy at 1 year post op and then every 3 years if no polyps
ASCO guidelines (Desch JCO 23:8512, 2005)
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Adjuvant Therapy of Stage III Colon Cancer: 3 year DFS
(equates with 5 year survival)
44%
63% 63% 64.20%
72.20%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Surgery
Lev/5FU
Leuc/5FU
Cape
FOLFOX