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ESMO Preceptorship Programme
Adjuvant treatment of colon cancer
Michel DUCREUX, MD, PhD
Gustave Roussy Cancer Centre, Grand Paris, FRANCE
Colorectal – Valencia – 18-19 May 2018
ESMO PRECEPTORSHIP PROGRAM
DISCLOSURE SLIDEParticipation to advisory boards:
ROCHE
MERCK SERONO
AMGEN
NOVARTIS
SANOFI
BAYER
SIRTEX
LILLY
SERVIER
IPSEN
2
Speaker in symposiums:
ROCHE
MERCK SERONO
NOVARTIS
IPSEN
LILLY
AMGEN
Research funding:
ROCHE
MERCK SERONO
PFIZER
My wife is the Head of The Oncology Business Unit in Sandoz Company (French Affiliate)
ESMO PRECEPTORSHIP PROGRAM
▪ Adjuvant chemotherapy is indicated for stage III (N+)
▪ FOLFOX / CapeOx ; 3 months vs 6 months
▪ Capecitabine or (inf.) FU/LV as an option for some patients
▪ FOLFOX / CapeOx for patients < 70y, use with caution for pts > 70y
▪ Antibodies (EGFR, VEGF) are not indicated
▪ The decision for an adjuvant treatment should balance the risk of
cancer mortality and that of comorbidities
▪ Specific problems
▪ Stage II
▪ Role of biological markers
Aims of the talk
STAGE III (N+)…
ESMO PRECEPTORSHIP PROGRAM
Sargent D, J Clin Oncol 2009Moertel et al NEJM 1990
10.3%
First positive study: 5FU +
levamisole…
ESMO PRECEPTORSHIP PROGRAM
X’Act trial (Capecitabine vs FuFol Mayo) Overall survival
Twelves C, N Engl J Med 2005
Non infériority < 0,001
Superiority 0,05Stage III colon
(n= 1987)
ESMO PRECEPTORSHIP PROGRAM
2004 combination chemotherapy!
FOLFOX new standard stage III
ESMO PRECEPTORSHIP PROGRAM
MOSAIC studyMain endpoint: Disease-Free Survival (3-years)
Secondary endpoint: tolerance, overall survival (6-years)
n=2246
Inclusion:
Oct 1998–Jan 2001 (146 centres;
20 countries)
• Colon cancer, complete resection
• Stage II, 40%; Stage III, 60%
• Age 18–75 years
• KPS ≥60
• No previous CT
RLV5FU2
FOLFOX4(LV5FU2 + oxaliplatin 85 mg/m²)
(n=1123)
(n=1123)
A. de Gramont et al., ASCO 2003 / T. André et al. NEJM 2004
ESMO PRECEPTORSHIP PROGRAMA. de Gramont et al., ASCO 2007 / T. André et al. JCO 2009
Data cut-off: January 2007 months
Pro
bab
ility
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
Events
FOLFOX4 243/1123 (21.6%)
LV5FU2 279/1123 (24.8%)
HR [95% CI]: 0.84 [0.71–1.00]
p=0.046
2,5%
FOLFOX4
LV5FU2
MOSAIC: Long-term results
Overall survival ITT
ESMO PRECEPTORSHIP PROGRAM
Long-term Tolerance
(% patients)
FOLFOX
5.5
LV5FU2
6.1
0
10
20
30
40
50
60
Pendant
Tx
6 mois 1-an 2-ans 3-ans 4-ans
Grade 1
Grade 2
Grade 3
Evaluable patients
n=976 4-year
Grade 0 85.5%
Grade 1 12.0%
Grade 2 2.8%
Grade 3 0.7%
Data cut-off: January 2007
Second cancer
Peripheral
Neuropathy
ESMO PRECEPTORSHIP PROGRAM
A. de Gramont et al., ASCO 2007 / T. André et al. JCO 2009Data cut-off: January 2007
FOLFOX4 stage II
LV5FU2 stage II
FOLFOX4 stage III
LV5FU2 stage III
Months
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 [0.70–1.41]
Stade III 0.80 [0.65–0.97]
0.1%
4.2%
p=0.986
p=0.023
Overall survival Stage II / III
XELOX
ESMO PRECEPTORSHIP PROGRAM
Stage III colon
cancer•No previous CT
• Resection ≤ 8 weeks
n=1886
n=944
n=942
RANDO MISATION
XELOX vs 5-FU/LV:
NO16968 (XELOXA) Phase III trial
Bolus 5-FU/LV (6 months) Mayo Clinic [n=664]*oru
Roswell Park [n=278]**
XELOX (6 months) Capecitabin 1000mg/m2
BID D1 to 14
(1 week rest)
+ oxaliplatin 130 mg/m2 IV D1
every 3 weeks
8 cycles
Main endpoint
Better DFS
ESMO PRECEPTORSHIP PROGRAM
Absolute difference at 3-year 4%
HR=0.80 (IC 95% : 0.69–0.93)
p=0.0045
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6 years
71 %
67 %
XELOX n=944 5-FU/LV n=942
Surv
ie s
ans
mal
adie
Schmoll et al. J Clin Oncol 2015;33:3733-40
Xelox, a valid option
Confirmed at 7 years : 63% vs 56%
ESMO PRECEPTORSHIP PROGRAM
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6
HR=0.87 (IC 95% : 0.72–1.05)
p= 0.1486
Years
78 %
74 %
XELOX n=9445-FU/LV n=942
Mean follow-up : 59 months
Surv
ie g
lob
ale
ITT population
Overall survival Xelox vs Fufol
Schmoll et al. J Clin Oncol 2015;33:3733-40Confirmed with longer follow-up: 73 vs 67%
ESMO PRECEPTORSHIP PROGRAM
64%CapecitabineX-ACT, 2005
65%LV5FU2MOSAIC 2004
61%LV5FU2André, 2003
66%FUFOL ou RPMIXELOXA, 2010
63%FUFOLINT0089, 2005
62%FUFOLIMPACT 1994
44%SurveillanceIMPACT 1993
52%SurveillanceMoertel 1990
3-y DFSTreatmentStudy
Monotherapy
73%
71%
FOLFOX4
XELOX
MOSAIC 2004
XELOXA, 2010
Poly CT
The last 15 years
A LITTLE BIT MORE
COMPLICATED…
ESMO PRECEPTORSHIP PROGRAM
Fluoropyrimidine ± Oxaliplatin Stage III
HR for DFS
P value DFS ∆ (%) HR for OS P valueOS ∆ (%)
MOSAIC (FOLFOX)
0.78CI, 0.65-0.93
@ 5 year
0.005∆ 7.5%
58.9% vs 66.4%@ 5 year
0.80CI, 0.65-0.97
@ 6 year
0.023∆ 4.2%
68.7% vs 72.9%@ 6 year
NSABP C-07(FLOX)
0.78CI, 0.68-0.90
@ 5 year
0.0007 ∆ 6.6 %57.8% vs 64.4%
@ 5 year
0.85CI, 0.72-1.00
@ 5 year
0.052∆ 2.7%
73.8% vs 76.5%@ 5 year
XELOXA(XELOX)
0.80CI, 0.69-0.93
@ 3 year
0.0045∆ 4.4%
66.5% vs 70.9%@ 3 year
0.87CI, 0.72-1.05
@ 5 year
0.1486∆ 3.4%
ND(57 months FU)
1 André T, J Clin Oncol. 2009
2 Yothers G, J Clin Oncol 2011
3 Haller D, J Clin Oncol 2011
ESMO PRECEPTORSHIP PROGRAM
Fluoropyrimidine ± Oxaliplatin Stage III HR for
DFSP value DFS ∆ (%) HR for OS P value
OS ∆ (%)
MOSAIC (FOLFOX)
0.78CI, 0.65-0.93
@ 5 year
0.005∆ 7.5%
58.9% vs 66.4%@ 5 year
0.80CI, 0.65-0.97
@ 6 year
0.023∆ 4.2%
68.7% vs 72.9%@ 6 year
NSABP C-07(FLOX)
0.78CI, 0.68-0.90
@ 5 year
0.0007 ∆ 6.6 %57.8% vs 64.4%
@ 5 year
0.85CI, 0.72-1.00
@ 5 year
0.052∆ 2.7%
73.8% vs 76.5%@ 5 year
XELOXA(XELOX)
0.80CI, 0.69-0.93
@ 5 year
0.004∆ 5 %
62% vs 67%@ 3 year
0.83CI, 0.70-0.99
@ 5 year
0.04∆ 3.0%74% vs. 77%
(@ 5y)
X-ACTFU/FA bolus vs.
Capecitabine
0.87CI, 0.75-1.00
@ 3y
0.0528∆ 3.6%
60.6% vs. 64.2%@ 3y
0.84 CI: 0.69–1.01
@3y
p=0.07∆ 3.7%
77.6% vs. 81.3%@3y
1 André T, J Clin Oncol. 2009
2 Yothers G, J Clin Oncol 2011
3 Haller D, J Clin Oncol 2011
4 Schmoll HJ, J Clin Oncol 2016
ESMO PRECEPTORSHIP PROGRAM
N 1-3
N > 3
Andre et al. JCO 2015
Overall survival stage III
pT3-4 N+
A ROLE FOR TARGETEDTHERAPIES?
ESMO PRECEPTORSHIP PROGRAM
Bevacizumab
3 large negative studies (>6000 pts)
- NSABP- C08- AVANT- QUASAR 2
ESMO PRECEPTORSHIP PROGRAM
NSABP C-08 trial
Phase III study
NSABP-C-08
Stage II/III
m FOLFOX 6 – 6 months
+ Bevacizumab -1 year
(n=1 335)
m FOLFOX 6 – 6 months
(n=1 338)
C. Allegra et al., ASCO 2011, A#3508
Stage II = 24.9%
Main endpoint: 3-year DFS
Median follow-up: 55 months
RR
ESMO PRECEPTORSHIP PROGRAM
NSABP-C-08: bevacizumab, no effect
C. Allegra et al., ASCO 2011, A#3508
100%
viv
ants
80
60
40
20
0
0 1 2 3 4 5
Years
1268
1289
1205
1233
1135
1163
942
950
204
204
mFF6 1341 Pts, 224 deaths
mFF6+Bev 1337 Pts, 218 deaths
HR=0.96, 95% CI (0.79-1.15)
p= 0.64
SG
Allegra C et al 2013;31:359-64
ESMO PRECEPTORSHIP PROGRAM
Cetuximab
2 large negative studies (>6000 pts)
- N0147- PETACC 8
ESMO PRECEPTORSHIP PROGRAM
KRAS WT
0
10
20
30
40
50
60
70
80
90
100
% S
urv
ivants
sans m
ala
die
0 6 12 18 24 30 36
Time (Months)
Folfox
Folfox + Cmab
Arm3 Year Rates
(95% CI)HR
(95% CI)P
Folfox
n=902
75.8%(72.1%-79.6%)
1.2(0.96-1.5)
0.22
Folfox+ Cmab
n=945
72.3%(68.5%-76.4%)
KRAS MT
0
10
20
30
40
50
60
70
80
90
100
% S
urv
ivants
sans m
ala
die
0 6 12 18 24 30 36
Time (Mointh)
Arm3 Year Rates
(95% CI)HR
(95% CI)P
Folfox
n=374
67.2%(61.4%-73.5%)
1.2(0.9-1.6)
0.13
Folfox+ Cmab
n=343
64.2%(58.7%-70.2%)
Folfox
Folfox + Cmab
NO 147: Folfox +/- cetuximab
Alberts et al. JAMA 2012;307:1383-93
ESMO PRECEPTORSHIP PROGRAM
FOLFOX4 + cetuximab
791 699 505 356 132 2 0
FOLFOX4811 732 527 381 131 4 0
PETACC8 : PFS : Wt KRAS
Years
DFS
rat
e
FOLFOX4 + CetuximabN = 791
FOLFOX4N = 811
No, events 190 179
S3-year PFS[95%CI], %
75.1[71.7; 78.1]
78.0[74.8; 80.8]
HR pour SSR [95% CI]p-value (log-rank)
1.047 [0.853; 1.286]O.6562
Taieb J et al Lancet Oncol 2014;15:862-73
ESMO PRECEPTORSHIP PROGRAM
Meta-analysis: nothing….
NEW DATA: A CHANGE IN THE
STANDARD OF CARE?
ESMO PRECEPTORSHIP PROGRAM
Heinemann, et al. ASCO 2014
*tumors of the transversum were excluded from
further analysis
3%*
44%
20%
77%
33%
Stage III
Stage IV
Stage II
Schrag et al. ASCO 2016
Prognostic role of tumour site
ESMO PRECEPTORSHIP PROGRAMSinicrope et al. Clin Cancer Res 2015
KRAS/BRAF wt
KRAS mut
BRAFmut
Biological features: a prognostic role
ESMO PRECEPTORSHIP PROGRAMSinicrope et al. Clin Gastroenterol Hepatol 2016;14:651–658
Interaction with MMR status
ESMO PRECEPTORSHIP PROGRAM
Role of the 4 classes of
molecular consensus???
Guinney et al. Nat Med 2015
ESMO PRECEPTORSHIP PROGRAM
Dienstmann R et al. Ann Oncol 2017;28:1023-31
Beyond TNM system??
• 8904 patients
• TNM, clinico-pathological featurs and biological determination of
Ras and Raf
• Training set: NO147 and PETACC 3
• Validation set: observational studies
Conclusion: Incorporation of MSI, BRAF and KRAS mutations improves the ability
to prognosticate in stage II and stage III cc patients, but only modestly increases
prediction accuracy in multivariate models that include clinicopathological
features, particularly in chemotherapy-treated patients…
3 MONTHS VERSUS 6
MONTHS… THE IDEA STORY…
ESMO PRECEPTORSHIP PROGRAM
IDEA Trials Summary
ESMO PRECEPTORSHIP PROGRAM
Non-inferiority Hypothesis Testing
ESMO PRECEPTORSHIP PROGRAM
Global IDEA study: toxicityAdverseEvents
FOLFOX CAPOX
G0 – 1 G2 G3 – 4 p-value G0 – 1 G2 G3 - 4 p-value
Global
ESMO PRECEPTORSHIP PROGRAM
Disease-free survival: primary
endpoint not met
Grothey A et al. 2018;378:1177-88
ESMO PRECEPTORSHIP PROGRAM
Primary DFS Analysis (mITT), cont.
Presented By Qian Shi at 2017 ASCO Annual Meeting
ESMO PRECEPTORSHIP PROGRAM
DFS in different subgroups of
patients
Grothey A et al. 2018;378:1177-88
ESMO PRECEPTORSHIP PROGRAM
DFS Forrest-plot….
Grothey A et al. 2018;378:1177-88
Grothey A et al. 2018;378:1177-88
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
High risk (T4 and / or N2)
~40%
Combined
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
High risk (T4 and / or N2)
~40%
62.7(60.8-64.4)
64.4(62.6-66.4)
1.12(1.03-1.23)
Combined
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
High risk (T4 and / or N2)
~40%
64.1(61.3-67.1)
64.0(61.2-67.0)
1.02(0.89-1.17)
61.5(58.9-64.1)
64.7(62.2-67.3)
1.20(1.07-1.35)
62.7(60.8-64.4)
64.4(62.6-66.4)
1.12(1.03-1.23)
Combined
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
83.1(81.8-84.4)
83.3(82.1-84.6)
1.01(0.90-1.12)
High risk (T4 and / or N2)
~40%
64.1(61.3-67.1)
64.0(61.2-67.0)
1.02(0.89-1.17)
61.5(58.9-64.1)
64.7(62.2-67.3)
1.20(1.07-1.35)
62.7(60.8-64.4)
64.4(62.6-66.4)
1.12(1.03-1.23)
Combined
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
85.0(83.1-86.9)
83.1(81.1-85.2)
0.85(0.71-1.01)
81.9(80.2-83.6)
83.5(81.9-85.1)
1.10(0.96-1.26)
83.1(81.8-84.4)
83.3(82.1-84.6)
1.01(0.90-1.12)
High risk (T4 and / or N2)
~40%
64.1(61.3-67.1)
64.0(61.2-67.0)
1.02(0.89-1.17)
61.5(58.9-64.1)
64.7(62.2-67.3)
1.20(1.07-1.35)
62.7(60.8-64.4)
64.4(62.6-66.4)
1.12(1.03-1.23)
Combined
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
3-year DFS (%)HR / CT
and subgroups
CT
XELOX FOLFOX XELOX/FOLFOX combined
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI)
SSR 3-year, % (95% CI) HR(95% CI) 3 m 6 m 3 m 6 m 3 m 6 m
Subgroups
Low risk(T1-3 N1)
~60%
85.0(83.1-86.9)
83.1(81.1-85.2)
0.85(0.71-1.01)
81.9(80.2-83.6)
83.5(81.9-85.1)
1.10(0.96-1.26)
83.1(81.8-84.4)
83.3(82.1-84.6)
1.01(0.90-1.12)
High risk (T4 and / or N2)
~40%
64.1(61.3-67.1)
64.0(61.2-67.0)
1.02(0.89-1.17)
61.5(58.9-64.1)
64.7(62.2-67.3)
1.20(1.07-1.35)
62.7(60.8-64.4)
64.4(62.6-66.4)
1.12(1.03-1.23)
Combined 75.9(74.2-77.6)
74.8(73.1-76.6)
0.95(0.85-1.06)
73.6(72.2-75.1)
76.0(74.6-77.5)
1.16(1.06-1.26)
P-value interaction test:CT: 0.0061
Risk-groups : 0.11
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
CT
XELOX FOLFOX
Riskgroups
Low-risk(T1-3 N1)
~60%3 months
High-risk(T4 et/ou N2)
~40%6 months
IDEA : Recommandations
Non-inferior Uncertain Inferior
ESMO PRECEPTORSHIP PROGRAM
CT
XELOX FOLFOX
Riskgroups
Low-risk(T1-3 N1)
~60%3 months (3-) 6 months
High-risk(T4 et/ou N2)
~40%3 (-6) months 6 months
IDEA : Recommandations
Non-inferior Uncertain Inferior
STAGE II DISEASE…. !!!!
ESMO PRECEPTORSHIP PROGRAM
Stage II
Small benefit (3%) with 5FU
No clear improvement with FOLFOX
Is-t possible to define a subgroupthat could benefit from FOLFOX?
ESMO PRECEPTORSHIP PROGRAM
Some Stage II tumours with poor
prognosis
0102030405060708090
100
5yr real OS (%)
Gunderson et al, JCO 2009
Stage II Stage III
ESMO PRECEPTORSHIP PROGRAM
QUASAR – old study, small benefit
ESMO PRECEPTORSHIP PROGRAMTournigand C et al. J Clin Oncol 2015;33:4176-87
MOSAIC : FOLFOX vs LV5FU2, all
stage II patients: no difference
ESMO PRECEPTORSHIP PROGRAMTournigand C et al. J Clin Oncol 2015;33:4176-87
Low risk High risk
MOSAIC late follow-up and Stage II
disease
ESMO PRECEPTORSHIP PROGRAM
Stage II
No risk factor
Stage II
Any risk
factor
O‘Connor et al. JCO 2011
Stage III
High risk stage
II and SEER
ESMO PRECEPTORSHIP PROGRAM
Overall 5-year survival
1950 colon cancer
– Groupe 1, occlusion without perforation n=120 33%
– Groupe 2, occlusion + perforation tumour n=35 50%
– Groupe 3, occlusion + proximal perforation n=13 33%
– Groupe 4, no occlusion, no perforation n=1682 51%
Do we even know how to select high
risk patients?
Chen et al, 2000
ESMO PRECEPTORSHIP PROGRAM
Low number of lymph nodes remains
not good… 134 567 pT3N0
< 12 LN analysed
– 23.3% of the patients
• 46.8% in 2003 – 12,5% en 2012
– 5-year overall survival : 66.8%
• 69.8% > 12 LN versus 58.7% p< 0.001
– 16.7% of adjuvant CT if less than 12 LN:
• OS with CT 78.4% versus 54.7% without, p< 0.001
Wells KO et al. Dis Colon Rectum 2017
ESMO PRECEPTORSHIP PROGRAM
Role of perineural invasion US National Database: 21,488 patients:
– 55.2% T3, 23.1% T2, 14.4% T1, 7.3% T4 disease
– 4.6% (n = 987) had PNI
– 86.8% no PNI and no CT; 8.7% no PNI and CT; 3.7% (n = 785) PNI and no
CT, and 0.9% (n = 202) PNI and CT
– Patients with PNI who had CT: younger, private insurance, fewer comorbidities greater T stage
– PNI and CT improved OS in T3-4 disease (P
ESMO PRECEPTORSHIP PROGRAM
No benefit in Stage III patients, could be even deleterious in stage II
patientsSargent DJ et al. J Clin Oncol. 2010;28:3219
MSI(n=165)
MSS(n=863)
Stage II Stage III
MSI + tumours, no benefit from 5FU
based CT
ESMO PRECEPTORSHIP PROGRAM
Coloprint, useful to select patients??
ESMO PRECEPTORSHIP PROGRAM
Immunoscore: an hope
ESMO PRECEPTORSHIP PROGRAM
Immunoscore and stage II disease:
DFSStage II (n=1433) - High/int/low
100
20
0
San
s re
chu
te (
%)
0 1 2 3 4 5 6
years7 24
375
694
364
p
ESMO PRECEPTORSHIP PROGRAM
Stage II colon cancer
Age < 70y Advanced age or
comorbidities
pT4 pT3
pMMR / MSS dMMR / MSI-H
Consider adj. CTx No adj. CTx
Additional marker:
less than 12 LN / PNI ? /
Gene signature / Immunoscore?
Algorithm of decision in stage II
disease
ESMO PRECEPTORSHIP PROGRAM
Stage III diseaseComplete resection
Reference
Folfox4 or Xelox
pT3N1 3 monthsXELOX
PT3N2 6 monthsXELOX or FOLFOX
> 70 y:
Capecitabine or LV5FU2
Options
CI oxaliplatin: LV5FU2 or cap
DPD measurebefore tmt
Adjuvant CT has to bediscussed