Identification of Predictive Biomarker in Metastatic Colorectal Cancer: ProfiLer Experience

Transcription

1 Identification of Predictive Biomarker in Metastatic Colorectal Cancer: ProfiLer Experience XIAOJUN JIANG MENTORS: OLIVIER TREDAN & JEAN-YVES BLAY

2 Collect 2000 tumors of all kinds of advanced cancer Collection of the available tumor sample + whole blood sampling Establishment of comprehensive genetic profiling (CGH Array and sequencing) Adapted therapeutic management based on the recommendations of molecular board 2

3 Ex: a patient diagnosed with glioblastoma 3

4 Regorafenib, Stivarga is a multi-kinase inhibitor with survival benefits in pts with pretreated mcrc, as demonstrated in the phase III CORRECT study. REG: 1 st multi-tyrosine kinase inhibitor in mcrc OS 1.5 months, PFS 0.2 months, Grade 3-4 toxicity +++ Long stable disease benefits. (PFS > 4 months) Right Drug for The Right Patient 4

5 Collection of the available tumor sample + whole blood sampling Establishment of comprehensive genetic profiling (CGH Array and sequencing) Adapted therapeutic management based on the recommendations of molecular board Collection of relevant clinical data of patients with advanced colorectal cancer 5

6 Patient General information; age at diagnosis; death; Family cancer history Other malignancy (site, histological type) Tumor Date of initial diagnosis, date of metastasis Site, histological type, initial TNM Treatment Operation date; Preoperative treatment; ptnm Postoperative chemotherapies (regimen type, T 0, each follow-up date, measure of response; date of treatment failure). Follow-ups. 6

7 Molecular profiling Routine - All RAS Statut, BRAF mutation - Microsatellite instability ProfiLER - Exon Sequencing of Selected Genes - CGH array Gain events: amplification/gain fort/gain/faible gain Loss events: délétion homozygote/interne/délétion Amplification Deletion 7

8 Hypothesis & Design 13 mcrc 1) patients 12 mccr et STS patients 100 patients mccr REBECCA CGH profiles of interested genes CGH profiles of interested genes Profilages des gènes cibles CR/PR/SD versus PD 1 ère validation 2 ème validation Test set Validation Set Interested genes: Genes encoding for the protein kinase targets of regorafenib 8

9 Target Heatmap Discovery Set Patients 13 mccr MTKI Regorafenib CR/PR/ SD PD Number 6 7 Average gain* Average loss Amplification Deletion 9

10 Validation set Validation Set Patients 7 mccr et 5 STS MTKI Regorafenib CR/PR/ SD PD Number 5 7 Average gain* Average loss Amplification Deletion 10

11 Overview TTC: Tumor Target Charge TTL: Tumor Target Loss 11

12 SCNA frequencies No difference in genomic index observed 12

13 SUMSCAN & Prognosis SUMSCAN Favorable SUMSCAN Unfavorable SUMSCAN predicts the survival benefits of regorafenib (HR: 0.42) OS (months) Favorable 8.9 Unfavorable

14 Key Messages 1. No association with response to chemotherapy 2. SUMSCAN Favorable Genomic instability 3. SUMSCAN predicts the survival benefits of REG. 14

15 Perspectives 2 nd step: 13 mcrc 1) patients 12 mccr et STS patients 100 patients mccr REBECCA CGH profiles of interested genes CGH profiles of interested genes Profilages des gènes cibles CR/PR/SD versus PD 1 ère validation 2 ème validation Cohorte de découverte Cohorte de validation REBECCA: ATU Cohort 15

16 Perspectives Perspectives Prospective Clinical Trial SUMSCAN Unfavorable: No regorafenib Application in other MTKIs 16

17 ACKNOWLEDGEMENTS Mentors Pr Jean Yves BLAY Dr Olivier TREDAN Translational Laboratory Daniel PISSALOUX Qing WANG Valéry ATTIGNON Marina ROUSSEAU-TSANGARIS Stéphanie COX Séverine TABONE-EGLINGER lyric.com «Grant INCa 4664» 17