Immunoscore clinical Colon Cancer Stage II pa …...Background Results Risk of relapse assessment...
Transcript of Immunoscore clinical Colon Cancer Stage II pa …...Background Results Risk of relapse assessment...
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
Copies of this poster obtained through Quick Response (QR) Code are for personal use only and may
not be reproduced without permission from ASCO® and the
author of this poster
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
60
80
100
0 1 2 3 4 5 6 7 8Time to recurrence (Years)
Patie
nts
with
out e
vent
(%)
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)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Time to recurrence (Years)
Patie
nts
with
out e
vent
(%)