1. Immunoscore Prognostic in Colon Cancer
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. Immunoscore in Colon Cancer
Conventional risk prediction methods for cancer provide little information on postoperative outcome[1,2]
Histopathologic tissue analysis focuses only on tumor cells
Host immune response not incorporated
Comprehensive evaluation of molecular features and immune reactions, including systemic and local immunologic biomarkers, critical for improving prognostic methods[1,2]
Immunoscore evaluates immune infiltrate in center and invasive margin of tumor and may be useful as prognostic marker[1,2]
Worldwide Immunoscore Consortium evaluated standardized Immunoscore assay in routine clinical settings[3]
1. Galon J, et al. J Transl Med. 2012;10: Galon J, et al. J Pathol. 2014;232: Galon J, et al. ASCO Abstract 3500.
Slide credit: clinicaloptions.com

3. Immunoscore in Colon Cancer: Study Design
Inclusion criteria
Colon cancer (excluding rectum cancer), stage I/II/III (T1-T4, N0-N2, M0)
No neoadjuvant treatments
Clinical data and follow-up
3855 pts quantified for Immunoscore study; 2667 analyzed after quality control and exclusion criteria
Primary endpoint: TTR for Immunoscore (high/low)
Secondary endpoint: TTR for Immunoscore (high/intermediate/low) all stages and stage II
Limitations: heterogeneity of pts between centers, in patient care between countries, in IHC staining, and in clinical data and follow-up between centers
TTR, time to recurrence.
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

4. Immunoscore in Colon Cancer: Study Design
Reference center sent SOP to all participating centers to standardize tissue collection and IHC procedures
Participating centers obtained tissue samples and performed IHC before sending data to reference center (in Europe) or clinical data center (in US)
External statistician analyzed all data using digital quantification of whole slide FFPE for 3 cohorts:
Training set
Internal validation set
External validation set
SOP, standard operating procedure.
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

5. Immunoscore in Colon Cancer: Pt Population
Characteristics
Training Set
(n = 700)
Internal Validation Set
(n = 636)
External Validation Set
(n = 969)
Median age, yrs
68.3 (±12.6)
68.3 (±12.2)
68.2 (± 32.7)
Male, n (%)
346 (49.4)
339 (53.3)
497 (51.3)
T stage, n (%) T1 T2 T3 T4
37 (5.3)
109 (15.6)
452 (64.6)
102 (14.6)
34 (5.3)
97 (15.3)
427 (67.1)
78 (12.3)
32 (3.3)
153 (15.8)
635 (65.5)
149 (15.4)
N stage, n (%) N0 N1 N2
508 (73.4)
124 (17.9)
60 (8.7)
482 (76.3)
107 (16.9)
43 (6.8)
608 (64.1)
223 (23.5)
117 (12.3)
Median lymph nodes, n
22.1 (±15.2)
21.8 (±16.9)
16.4 (±11.8)
Proximal colon cancer, n (%)
Distal colon cancer, n (%)
Missing, n (%)
349 (49.9)
2 (0.3)
307 (48.3)
327 (51.5)
1 (0.2)
527 (54.9)
431 (44.9)
2 (0.2)
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

6. Immunoscore in Colon Cancer: Pt Population
Characteristics
Training Set
Internal Validation Set
External Validation Set
Time to end of follow-up
Median survival, mos
5-yr survival rate, %
( )
74.9 ( )
( )
77.8 ( )
( )
68.8 ( )
Recurrence-free survival time
( )
68.3 ( )
( )
71.3 ( )
95.1 ( )
58.3 ( )
All multivariate models adjusted for Immunoscore, age, sex, T stage,
N stage, and stratified by city center
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

7. Immunoscore in Colon Cancer: Time to Recurrence, Training Set
Outcome
Training Set
High
Intermediate
Low
Primary objective (high/low):
5-yr time to recurrence, % (95% CI)
67.3
( ) --
85.3
( )
HR (95% CI)
0.41 ( )
P value
C-index
< .0001
0.60
Secondary objective (high/int/low):
81.9
( )
92.3
( )
Int vs high: 0.51 ( )
Low vs high: 0.19 ( )
0.64
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

8. Internal Validation Set
Immunoscore in Colon Cancer: Time to Recurrence, Internal Validation Set
Outcome
Internal Validation Set
High
Intermediate
Low
Primary objective (high/low):
5-yr time to recurrence, % (95% CI)
74.3
( ) --
88.0
( )
HR (95% CI)
0.41 ( )
P value
C-index
< .0001
0.60
Secondary objective (high/int/low):
86.1
( )
91.4
( )
Int vs high: 0.48 ( )
Low vs high: 0.27 ( )
.0001
0.63
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

9. External Validation Set
Immunoscore in Colon Cancer: Time to Recurrence, External Validation Set
Outcome
External Validation Set
High
Intermediate
Low
Primary objective (high/low):
5-yr time to recurrence, % (95% CI)
58.3
( ) --
76.2
( )
HR (95% CI)
0.51 ( )
P value
C-index
< .0001
0.56
Secondary objective (high/int/low):
72.0
( )
83.1
( )
Int vs high: 0.62 ( )
Low vs high: 0.33 ( )
0.60
CI, confidence interval; FRS, recurrence free survival.
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

10. Immunoscore in Colon Cancer: Secondary Objectives Efficacy Endpoints
Outcome
High
Intermediate
Low
5-yr time to recurrence, % (95% CI)
69.0
( )
80.6
( )
88.9
( )
HR (95% CI)
P value
Int vs high: 0.58 ( )
Low vs high: 0.29 ( )
< .0001
5-yr DFS, % (95% CI)
57.6
( )
69.2
( )
75.4
( )
Int vs high: 0.69 ( )
Low vs high: 0.52 ( )
5-yr OS, % (95% CI)
66.9
( )
77.3
( )
81.5
( )
Int vs high: 0.73 ( )
Low vs high: 0.59 ( )
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

11. Immunoscore in Colon Cancer: Conclusions
Primary endpoint reached: TTR significantly longer in pts with high Immunoscore at all stages
Significance remained in multivariate analysis in all cohorts (TS, IVS, EVS)
Immunoscore predicts TTR, DFS, and OS
Base on findings, authors suggest that Immunoscore may be incorporated as new classification for cancer, TNM- Immune (TNM-I)
First standardized immune-based assay for classifying cancer, which authors suggest may help to individualize immunotherapy in the future
EVS, external validation set; DFS, disease-free survival; IVS, internal validation set; TS, training set; TTR, time to recurrence.
Slide credit: clinicaloptions.com
Galon J, et al. ASCO Abstract 3500.

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