Decipher Bladder Predicts Which Patients May Benefit from Neoadjuvant Chemotherapy Prior to Radical Cystectomy

Transcription

1 Decipher Bladder Predicts Which Patients May Benefit from Neoadjuvant Chemotherapy Prior to Cystectomy Contact the GenomeDx Customer Support Team (toll-free) DecipherTest.com

2 IDENTIFIES PATIENTS WHO MAY BE Decipher Bladder is used to classify a patient s bladder tumor into one of four molecular subtypes. Each molecular subtype has a distinct prognosis and is associated with benefit or non-benefit from neoadjuvant chemotherapy (NAC). Bladder Molecular Subtypes 1 Infiltrated Claudin-Low Favorable prognosis compared to other molecular subtypes Limited response to NAC Limited response to NAC Consider for immunotherapy trials Unfavorable prognosis Substantial benefit from NAC Unfavorable prognosis May benefit from NAC Consider for clinical trials Suggested Patient Management Diagnosis of Muscle Invasive Bladder Cancer Order Decipher Bladder Infiltrated Patient s tumor is classified into one of four subtypes Claudin-Low

3 NEFIT FROM NEOADJUVANT CHEMOTHERAPY PRIOR TO SURGERY Unmet Need : Which muscle invasive bladder cancer patients will benefit from neoadjuvant chemotherapy? molecular subtype patients experienced ~30% survival benefit from NAC and Infiltrated molecular subtypes did NOT experience significant survival benefit from NAC 1 Solution Decipher Bladder determines the molecular subtype with high accuracy for an individual patient tumor and informs which patients with muscle invasive bladder cancer may benefit from neoadjuvant chemotherapy. Decipher Bladder Test Indications Specimen Type: TURBT (Transurethral Resection of Bladder Tumor) (FFPE) Tumor Type: Muscle Invasive Carcinoma Primary Histology Type: Urothelial/Transitional Cell Carcinoma No Evidence of Distant Metastasis No Prior Neoadjuvant Chemotherapy Plan Guided by Decipher Bladder Cystectomy 1 Cystectomy 1 Clinical Trials of Immunotherapies 2 Neoadjuvant Chemotherapy 1 Cystectomy 1 Neoadjuvant Chemotherapy 1 Cystectomy 1 Clinical Trials of Novel Agents 1

4 Patients with basal subtype tumors experienced greatest survival benefit when treated with neoadjuvant chemotherapy as compared to surgery alone. No Neoadjuvant Chemotherapy n=476 1 With Neoadjuvant Chemotherapy n= p < p = Overall Survival Infiltrated Claudin-Low Time, months Overall Survival Infiltrated Claudin-Low Time, months tumor patients may be prioritized for neoadjuvant chemotherapy as they gain the most overall survival (OS) benefit Claudin-Low tumor patients did poorly, but saw slight improvement in OS with neoadjuvant chemotherapy or Infiltrated tumor patients had similar survival with or without neoadjuvant chemotherapy subtype patients had favorable prognosis overall. 3-Year Overall Survival Post Cystectomy vs. Cystectomy + Neoadjuvant Chemotherapy 1 Subtype Cystectomy (n=476)* Cisplatin-based Neoadjuvant Chemotherapy + Cystectomy (n=269)** 76.6% 74.7% Infiltrated 59.4% 50.6% 49.2% 77.8% Claudin-Low *p<0.0001; **p= % 57.9%

5 Decipher Bladder classifies into one of four molecular subtypes to guide personalized therapeutic decision making Subtype Interpretation 1 Limited benefit from neoadjuvant chemotherapy May be considered for immediate radical cystectomy Infiltrated Limited benefit from neoadjuvant chemotherapy May be considered for immediate radical cystectomy and enrollment into immunotherapy trials 2 Substantial benefit from neoadjuvant chemotherapy May be prioritized to neoadjuvant chemotherapy Claudin-Low May benefit from neoadjuvant chemotherapy May be considered for neoadjuvant chemotherapy and enrollment into clinical trials of novel agents Background: About Decipher Bladder 1 Developed on the same Decipher GRID platform as Decipher Post-Op and Biopsy for prostate cancer Measures mrna expression levels of 149 genes used to determine probabilities of the tumor sample belonging to each of the four molecular subtypes AUCs ranging from 0.85 to 0.97 for classifying a tumor sample into one of the four molecular subtypes Decipher Bladder has been developed and validated in 305 neoadjuvant chemotherapy and 476 radical cystectomy alone patients from 10 leading cancer centers in North America and Europe, including University of British Columbia, University of Bern, University of Washington and UC Davis

6 Decipher Bladder Report GenomeDx Biosciences Laboratory Science Center Dr. Suite 240, San Diego, CA Tel: l Fax: customersupport@genomedx.com l Patient Details: Patient Name: MRN/Patient ID #: Date of Birth: Gender: Pathology Laboratory: Pathologist: Address: TURBT Specimen Order Information: Order Date: Specimen Received Date: GenomeDx Accession ID: Specimen ID: Ordering Physician: Clinic/Hospital Name: Clinic/Hospital Address: Additional Physician: Clinical Details Date of TURBT: 12 / 01 / 2016 Tumor Type: Tumor Grade: Muscle Invasive Carcinoma with Carcinoma In-Situ High Grade Histology Type: Lymph-Vascular Invasion: Urothelial / Transitional Cell Carcinoma Not Identified Bladder Your Decipher Result Infiltrated Subtype Subtype Subtype Probability Interpretation 2% Patients may be considered for immediate radical cystectomy Favorable prognosis following surgery and may have limited benefit from cisplatin-based neoadjuvant chemotherapy 1,2 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was similar to those with surgery alone 2 Infiltrated 94% Patients may be considered for immediate radical cystectomy and enrollment into immunotherapy clinical trials Unfavorable prognosis and may have limited benefit from cisplatin-based neoadjuvant chemotherapy 2,3 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was similar to those with surgery alone 2 Patients with this subtype have been shown to most likely benefit from anti-pd-l1 immunotherapy in the locally advanced and metastatic setting 4 1% Patients may be prioritized to cisplatin-based neoadjuvant chemotherapy Unfavorable prognosis but may receive substantial benefit from cisplatin-based neoadjuvant chemotherapy 1,2 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was substantially higher than those with surgery alone 2 Claudin-Low 3% Patients may be considered for cisplatin-based neoadjuvant chemotherapy and enrollment into clinical trials of novel agents Unfavorable prognosis and may benefit from cisplatin-based neoadjuvant chemotherapy 2,5 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was moderately higher than those with surgery alone 2 References on reverse Assay Description. Decipher Genomic Subtyping Classifier (GSC), a microarray gene expression assay is used to classify formalin-fixed paraffin-embedded (FFPE) bladder tumor samples into one of four molecular subtypes (, Infiltrated,, Claudin-Low) based on functional molecular pathways. The GSC has been developed and validated in 305 neoadjuvant chemotherapy and 476 radical cystectomy alone patients from 10 leading cancer centers in North America and Europe. GSC measures RNA expression levels of 149 genes used to calculate multinomial probabilities of the tumor sample belonging to each of the four molecular subtypes. The higher the score, the more certain the sample will belong to assigned subtype. The patient tumor samples are classified as belonging to the subtype with the highest probability. The Decipher GSC molecular subtypes are based on a consensus classification derived from The Cancer Genome Atlas project and other previously published schema. 1,6-8 The GSC has AUCs ranging from 0.85 to 0.97 for classifying a tumor sample into one of the four molecular subtypes in two independent validation cohorts (n=558). 2 GenomeDx Medical Director (Name & Signature) Medical Directors: Timothy J. Triche, MD, PhD Doug Dolginow, MD Date Disclaimer: The Decipher test was developed and its performance characteristics were determined by GenomeDx Biosciences Laboratory. The GenomeDx Biosciences Laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) to perform high complexity testing. This test has not been cleared or approved by the U.S. Food and Drug Administration. Summary of surgical pathology report provided for convenience of Ordering Physician. Please refer to Referring Pathologist s original pathology report to guide treatment decisions. CLIA ID# 05D Rev: Copyright GenomeDx Biosciences Inc. Page 1 of 2

7 Decipher Bladder Report GenomeDx Biosciences Laboratory Science Center Dr. Suite 240, San Diego, CA Tel: l Fax: customersupport@genomedx.com l Patient Details: Patient Name: MRN/Patient ID #: Date of Birth: Gender: Pathology Laboratory: Pathologist: Address: TURBT Specimen Order Information: Order Date: Specimen Received Date: GenomeDx Accession ID: Specimen ID: Ordering Physician: Clinic/Hospital Name: Clinic/Hospital Address: Additional Physician: Clinical Details Date of TURBT: 12 / 01 / 2016 Tumor Type: Tumor Grade: Muscle Invasive Carcinoma with Carcinoma In-Situ High Grade Histology Type: Lymph-Vascular Invasion: Urothelial / Transitional Cell Carcinoma Not Identified Bladder Your Decipher Result Subtype Subtype Subtype Probability Interpretation 1% Patients may be considered for immediate radical cystectomy Favorable prognosis following surgery and may have limited benefit from cisplatin-based neoadjuvant chemotherapy 1,2 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was similar to those with surgery alone 2 Infiltrated 2% Patients may be considered for immediate radical cystectomy and enrollment into immunotherapy clinical trials Unfavorable prognosis and may have limited benefit from cisplatin-based neoadjuvant chemotherapy 2,3 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was similar to those with surgery alone 2 Patients with this subtype have been shown to most likely benefit from anti-pd-l1 immunotherapy in the locally advanced and metastatic setting 4 93% Patients may be prioritized to cisplatin-based neoadjuvant chemotherapy Unfavorable prognosis but may receive substantial benefit from cisplatin-based neoadjuvant chemotherapy 1,2 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was substantially higher than those with surgery alone 2 Claudin-Low 4% Patients may be considered for cisplatin-based neoadjuvant chemotherapy and enrollment into clinical trials of novel agents Unfavorable prognosis and may benefit from cisplatin-based neoadjuvant chemotherapy 2,5 3-year overall survival for these patients with cisplatin-based neoadjuvant chemotherapy was moderately higher than those with surgery alone 2 References on reverse Assay Description. Decipher Genomic Subtyping Classifier (GSC), a microarray gene expression assay is used to classify formalin-fixed paraffin-embedded (FFPE) bladder tumor samples into one of four molecular subtypes (, Infiltrated,, Claudin-Low) based on functional molecular pathways. The GSC has been developed and validated in 305 neoadjuvant chemotherapy and 476 radical cystectomy alone patients from 10 leading cancer centers in North America and Europe. GSC measures RNA expression levels of 149 genes used to calculate multinomial probabilities of the tumor sample belonging to each of the four molecular subtypes. The higher the score, the more certain the sample will belong to assigned subtype. The patient tumor samples are classified as belonging to the subtype with the highest probability. The Decipher GSC molecular subtypes are based on a consensus classification derived from The Cancer Genome Atlas project and other previously published schema. 1,6-8 The GSC has AUCs ranging from 0.85 to 0.97 for classifying a tumor sample into one of the four molecular subtypes in two independent validation cohorts (n=558). 2 GenomeDx Medical Director (Name & Signature) Medical Directors: Timothy J. Triche, MD, PhD Doug Dolginow, MD Date Disclaimer: The Decipher test was developed and its performance characteristics were determined by GenomeDx Biosciences Laboratory. The GenomeDx Biosciences Laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) to perform high complexity testing. This test has not been cleared or approved by the U.S. Food and Drug Administration. Summary of surgical pathology report provided for convenience of Ordering Physician. Please refer to Referring Pathologist s original pathology report to guide treatment decisions. CLIA ID# 05D Rev: Copyright GenomeDx Biosciences Inc. Page 1 of 2

8 Based on a patient s personal tumor genomics, Decipher Bladder: Identifies which bladder cancer patients may benefit from neoadjuvant chemotherapy prior to radical cystectomy Classifies bladder tumors into one of four molecular subtypes with distinct treatment implications regarding response to neoadjuvant chemotherapy Infiltrated Claudin-low Immune cells 4 layer layer Muscle tissue Access for All Patients All insurance plans accepted Proven and comprehensive financial assistance for patients References 1. Seiler, R., et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival outcome to neoadjuvant chemotherapy: results from a multi-institutional validation study. Presented at the Annual Meeting of the Society of Urologic Oncology, Rosenberg, J.E. et al., Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. The Lancet 2016; 387, 10031: Decipher Bladder is developed and run on the same Decipher GRID technology platform as in Decipher prostate. Shortly, the GRID research program will provide access to an in-depth, personalized Bladder Tumor RNA Expression Profile for your Decipher Patient. This research use only (RUO) information can provide valuable insights. In addition, the GRID research program aims to foster collaborations among researchers by collectively sharing this wealth of data to facilitate new genomic discoveries. To learn more, visit DecipherGRID.com. Robust and Prolific Technology Platform Archived FFPE tissue Whole Genome Technology Genomic analysis of 1.4 million biomarkers To learn more about Decipher, contact the GenomeDx Customer Support Team at (toll free) or at customersupport@genomedx.com or visit DecipherTest.com. Copyright 2017 GenomeDx Biosciences Inc. DBDR