ResultsBackgroundRisk of relapse assessment and survival predic�onIn the interna�onal valida�on (Pagès et al. Lancet 2018), of all clinical parameters, therela�ve contribu�on to the risk showed that Immunoscore (47%) was be�er than TNMstaging (28%), grade of differen�a�on (15%), VELIPI (8%), sex (<3%), mucinous, and MSIstatus. Immunoscore was stronger than all these clinical parameters, showing the highestcontribu�on to predict survival:

MethodAnalyses of Immunoscore (High/Low) using pre-defined cut-offs, blinded to clinicaloutcome:Kaplan-Meier analyses for 5Y TTR were performed on St II subgroups (see Pa�entsCharacteris�cs) from the Immunoscore interna�onal valida�on study (Pagès et al. Lancet2018).

Pa�ents were classified in 2 categories using pre-defined cutoffs: Low Immunoscore (0-1) vsHigh Immunoscore (2-3-4).

Introduc�onRisk assessment is par�cularly important to decide when to propose an adjuvant treatmentfor Stage (St) II CC pa�ents. High-risk St II pa�ents defined as those with poor prognos�cfeatures (T4, lymph nodes sampling <12, poor differen�a�on, VELIPI, bowel obstruc�on orperfora�on) can be considered for adjuvant chemotherapyImmunoscore® is an IVD test predic�ng the risk of relapse in early-stage Colon Cancer (CC)pa�ents, by measuring the host immune response at the tumor site. It is a risk-assessmenttool providing independent and superior prognos�c value than the usual tumor riskparameters and is intended to be used as an adjunct to the TNM classifica�on.In the present study, we inves�gated Immunoscore clinical performance within subgroups ofthe St II pa�ents included in the interna�onal SITC-led valida�on study (Pagès et al. Lancet2018), in par�cular to iden�fy pa�ents who could be spared chemotherapy.

Conclusions• Among High-risk untreated St II pa�ents: 69.5% had a High Immunoscore

with 5Y TTR of 87.4% (95% CI 83.9-91.0), significantly superior to the 5YTTR of the Low Immunoscore pa�ents (72.2% (95% CI 65.6-79.6))(p<0.00001)

• Among untreated St II pa�ents: the 5Y TTR observed in the HighImmunoscore High-risk group (87.4%) is sta�s�cally similar to the 5Y TTRobserved in the Low-risk group: 89.1% (95% CI 86.1-92.1) (p=0.42)

• Within High-risk St II pa�ents, 5Y TTR in pa�ents with a High Immunoscoreis similar in untreated pa�ents and pa�ents who received adjuvantchemotherapy (5Y TTR of 83.4 (95% CI 77.6-89.9)) (p=0.37)

Despite the presence of high-risk clinico-pathological features that usuallytrigger adjuvant treatment, when not treated with chemotherapy, thisretrospec�ve study indicates that a significant part of these pa�ents (69.5%)with high-Immunoscore, had a recurrence risk similar to the untreated lowrisk pa�ents.

This study reinforces Immunoscore clinical u�lity to guide adjuvanttreatment decisions in Stage II pa�ents.

References• Pagès F, Mlecnik B, Marliot F et al. Interna�onal valida�on of the consensus Immunoscore for the

classifica�on of colon cancer: a prognos�c and accuracy study. Lancet. 2018; 391 (10135)

• Sinicrope F, Shi Q, Hermitte F et al. Immunoscore to provide prognos�c informa�on in low- (T1-3N1)and high-risk (T4 or N2) subsets of stage III colon carcinoma pa�ents treated with adjuvant FOLFOX ina phase III trial (NCCTG N0147; Alliance). J Clin Oncol. 2018; 36:4s (suppl; abstr 614)

• Sinicrope F, Shi Q, Hermitte F et al. Associa�on of immune markers and Immunoscore with survival ofstage III colon carcinoma (CC) pa�ents (pts) treated with adjuvant FOLFOX: NCCTG N0147 (Alliance).J Clin Oncol. 2017; 35:15s (suppl; abstr 3579)

• Nitsche U, Stöss C, Friess H. Effect of Adjuvant Chemotherapy on Elderly Colorectal Cancer Pa�ents:Lack of Evidence. Gastrointest Tumors. 2017; 4(1-2)

• Mlecnik B, Bindea G, Angell HK et al. Integra�ve Analyses of Colorectal Cancer Show Immunoscore Isa Stronger Predictor of Pa�ent Survival Than Microsatellite Instability. Immunity.2016;15;44(3)

Pagès et al. Lancet 2018

Pa�ents characteris�csIni�al cohort: n= 2267 colon cancer pa�ents (Stage I/II/III), pre-defined Immunoscore cut-offs (Pagès et al. Lancet 2018)

Pa�ents were considered High-risk Stage II if they had at least 1 of the following clinico-pathological high-risk features:

Test principle

Immune InfiltrateCD3+ and CD8+ cell

density

Predic�ve of risk of relapse *

IS Low IS Intermediate IS High

IS 2IS 0 IS 1 IS 3 IS 4

* Based on the interna�onal Immunoscore SITC study results (2681 CC pa�ents samples) Pagès et al. Lancet 2018.

Immunoscore

CD3 CD3 CD3CD8 CD8CD8

High-risk Medium risk Low-risk

Jérôme Galon1, Fabienne Hermi�e2, Bernhard Mlecnik3, Florence Marliot1,4, Carlo Bifulco5, Alessandro Lugli6, Iris D Nagtegaal7, Arndt Hartmann8, Marc Van den Eynde9, Michael H A Roehrl10, Pamela S Ohashi11, Eva Zavadova12, Toshihiko Torigoe13, Prabhu S Patel14, Yili Wang15, Yutaka Kawakami16, Francesco M Marincola17, Paolo A Ascierto18, Bernard A Fox19, Franck Pagès1,4

1- INSERM, Laboratory of Integra�ve Cancer Immunology, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot; Centre de Recherche des Cordeliers, Paris, FR | 2- R&D, HalioDx, Marseille, FR | 3- Inovarion, Paris, FR | 4- Laboratory of Immunology, AP-HP, Georges Pompidou European Hospital, Paris, FR | 5- Department of Pathology, Providence Portland Medical Center, Portland, OR, US | 6- Ins�tute of Pathology, University of Bern, Bern, CH | 7- Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, NL | 8- Department of Surgery,University Erlangen-Nürnberg, Erlangen, DE | 9- Department of Medical Oncology, Cliniques Universitaires St. Luc, Brussels, BE | 10- Department of Pathology, Memorial Sloan Ke�ering Cancer Center, New-York, NY, US | 11- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CA | 12- Pathology, General Faculty Hospital, VFN Charles University, Prague, CZ| 13- Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, JP | 14- Cancer Biology, The Gujarat Cancer & Research Ins�tute, Ahmedabad, IN | 15- Ins�tute for Cancer Research, School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xian, CN | 16- Division of Cellular Signaling, Ins�tute for Advanced Medical Research, Keio University School of Medicine, Tokyo, JP | 17- Immune oncology discovery, AbbVie Inc., Redwood City, CA, US | 18- Melanoma, Cancer Immunotherapy and Innova�ve TherapyUnit, Is�tuto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Napoli, IT | 19- Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Ins�tute at the Robert W. Franz Cancer Center, Portland, US.

Immunoscore clinical u�lity to iden�fy good prognos�c Colon Cancer Stage II pa�ents with high-risk clinico-pathological features for whom adjuvant treatment may be avoided

Gastrointes�nal Cancers Symposium 2019

T4 tumors Lymph nodes sampling <12 Poorly differen�ated tumor Lympha�c/vascular or perineural

invasion Bowel obstruc�on or perfora�on

High-risk stage II

Low-Immunoscore High-Immunoscore

Colon cancer pa�ents

Surgery Immuno-pathology : Immunoscore I-TNM classifica�on

High-Immunoscore

≥70+ years

Chemotherapy recommenda�on

Consider Avoiding

Consider Avoiding(possibly detrimental)

Consider

Tradi�onal risk assessment

Immunoscore

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Time to recurrence in High-Risk Stage II CC pa�ents based on ImmunoscoreStage II untreated (no chemotherapy) pa�ents

High-risk Stage II pa�ents (based on clinico-pathological high-risk features) but with High-Immunoscore have good clinical outcome (similar to Low-risk pa�ents)

Among the pa�ents with high-risk features (n=630), 438 (69.5%) had aHigh Immunoscore with a corresponding 5Y TTR of 87.4 (95% CI 83.9-91.0), sta�s�cally similar (logrank pv not stra�fied p>0.42, wald pvstra�fied by center p>0.20) to the TTR 89.1 (95% CI 86.1-92.1)observed for the 500 Low-risk pa�ents (with no clinico-pathologicalfeature).

Time to recurrence in Stage II CC pa�ents based on Immunoscore and chemotherapyStage II pa�ents ≥ 70 years, chemo vs no chemo

In this cohort, 5Y TTR in St II pa�ents ≥ 70 years with HighImmunoscore who did not receive chemotherapy was be�er thanin those who received chemotherapy.

Within St II pa�ents with high-risk features, 5Y TTR in pa�ents with a High Immunoscore is similar in untreated pa�ents (n=438) and pa�ents who received adjuvant chemotherapy (n=162) (5Y TTR of 83.4 (95% CI 77.6-89.9)) (p=0.37).

TTR according to the clinico-pathological risk categories (High Risk vs Low Risk) and Immunoscore (IS 0-1 vs IS 2-3-4) in untreated Stage II colon cancer pa�ents (n=1130)

TTR according to administra�on of adjuvant chemotherapy (Chemo vs No Chemo) and to the Immunoscore (IS 0-1 vs IS 2-3-4) in High-risk Stage II colon cancer pa�ents (n=874)

TTR according to administra�on of adjuvant chemotherapy (Chemo vs No Chemo) and to the Immunoscore (IS 0-1 vs IS 2-3-4) in elderly Stage II colon cancer pa�ents (all risk categories n=679)

Rela�ve importance of each risk parameter to survival risk using the χ² propor�on test for clinical parameters plus Immunoscore in Stage II pa�ents with high-risk feature(s) (n=286 (data available on MSI status and other clinico-pathological parameters))

Treatment decisions in High-Risk St II colon cancer pa�entsNo randomized trial has been conducted to demonstrate a poten�al benefit ofchemotherapy to High-risk Stage II Colon Cancer pa�ents.However, High-risk Stage II pa�ents defined as those with poor prognos�c clinico-pathologic features are typically considered for adjuvant chemotherapy.These risk features are imperfect and addi�onal risk factors are needed to guidetreatment decisions.

Treatment decisions in St II Elderly pa�ents• The median age at the �me of CRC diagnosis is 68 years

• However, clinical studies that evaluated the effect of adjuvant treatment regimens havea selec�on bias in favor of younger pa�ents

• The benefit of adjuvant treatment in the elderly pa�ents is s�ll unclear

Fig. 1

Fig. 2

Fig. 4Fig. 3

High-risk Stage II pa�ents, chemo vs no chemo

Subgroups:

Stage II colon cancer untreated pa�ents(no chemotherapy) : n= 1130

• Low-risk untreated Stage II pa�ents:n=500

• High-risk untreated Stage II pa�ents:n=630

Stage II High-risk: n=874(chemo n=244 vs no chemo n=630)

Stage II elderly pa�ents ≥70 years,all risk categories (n=679)

Immunoscore shows the highest contribu�on to predict survival(60%, stronger than all the other parameters).

Low-Risk Patients: 50/500 (44.25%) 5Y: 89.1 (86.1-92.1)

0

20

40

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0 1 2 3 4 5 6 7 8Time to recurrence (Years)

Patie

nts

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(%)

Low-Risk

High-Risk IS 0-1

High-Risk IS 2-3-4

High-Risk IS 0-1 Patients: 49/192 (16.99%) 5Y: 72.2 (65.6-79.6)High-Risk IS 2-3-4 Patients: 49/438 (38.76%) 5Y: 87.4 (83.9-91)

NO CHEMO IS 0-1

NO CHEMO IS 2-3-4CHEMO IS 0-1CHEMO IS 2-3-4

NO CHEMO IS 0-1 Patients: 33/145 (21.35%) 3Y: 79 (72.1−86.6)

NO CHEMO IS 2-3-4 Patients: 44/454 (66.86%) 3Y: 90.6 (87.6−93.7)

CHEMO IS 0-1 Patients: 6/29 (4.27%) 3Y: 78.7 (64.9−95.4)

CHEMO IS 2-3-4 Patients: 11/51 (7.51%) 3Y: 78.5 (67.5−91.3)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8Time to recurrence (Years)

Patie

nts

with

out e

vent

(%)

NO CHEMO IS 0-1

NO CHEMO IS 2-3-4

CHEMO IS 0-1

CHEMO IS 2-3-4

NO CHEMO IS 0-1 Patients: 49/192 (21.97%) 5Y: 72.2 (65.6−79.6)

NO CHEMO IS 2-3-4 Patients: 49/438 (50.11%) 5Y: 87.4 (83.9−91)

CHEMO IS 0-1 Patients: 20/82 (9.38%) 5Y: 73.6 (64.3−84.2)

CHEMO IS 2-3-4 Patients: 24/162 (18.54%) 5Y: 83.4 (77.6−89.8)

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0 1 2 3 4 5 6 7 8Time to recurrence (Years)

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(%)