GENOMICS PERSONALIZED CANCER TREATMENT

GENOMICS PERSONALIZED CANCER TREATMENT 1 ABOUT PRECISION GENOMICS Intermountain Precision Genomics™ is on the forefront of personalized cancer tes...
8 downloads 2 Views 10MB Size
GENOMICS PERSONALIZED CANCER TREATMENT

1

ABOUT PRECISION GENOMICS

Intermountain Precision Genomics™ is on the forefront of personalized cancer testing for all types of genetic mutations.

TABLE OF CONTENTS 4.................................. ABOUT PRECISION GENOMICS 6.................................. BENEFITS FOR PATIENTS 8.................................. TESTING TIMELINE 10................................ SAMPLE REPORT 12................................ N-OF-ONE ADVANTAGES 14................................ PUBLISHED ABSTRACTS 16................................ CLINIC PATHWAYS 18................................ LABORATORY INFORMATION 20................................ FREQUENTLY ASKED QUESTIONS 22................................ HOW TO ORDER

2

3

ABOUT PRECISION GENOMICS

A NEW WAY OF TREATING CANCER

Intermountain Precision Genomics™ is distinctively positioned to advance research and monitor outcomes. We are the only entity that tests, treats, measures and improves outcomes (including survival, cost, and side effect reduction). We own the nation’s largest biorepository, which stores more than three million tissue samples used for the advancement of cancer (and other) research.

CUSTOMIZED TESTING WITHOUT THE TRAVEL Intermountain Precision Genomics™

THE ONLY PROVIDER OFFERING TESTING AND TREATMENT 

provides services to any oncologist,

Intermountain Precision Genomics™ in-house laboratory analyzes the DNA and

regardless of where the practice is

genetic makeup of a cancer patient’s tumor. We are the only healthcare system

located or where the patient resides.

in the nation with the capability to test and provide treatment for all possible gene mutation types. Because of this, patients have a dramatically improved chance for discovery of a treatable gene mutation. Nearly 80% of our patients have been connected to targeted therapies. No other healthcare system has comparable success.

PERSONALIZED CANCER TREATMENT

Intermountain Precision Genomics™ is on the forefront of personalized cancer testing for all types of genetic mutations. Our process is unique because we offer a Molecular Tumor Board review as a part of every test. This team

Ordering a test is simple. It only takes an average of 14 days to receive a detailed report indicating any known variants and recommended treatment options from our Molecular Tumor Board.

approach gives community oncologists confidence in providing the best options for patients. Drug procurement is also available and clinical trial information is included in the results. 4

5

BENEFITS FOR PATIENTS

GIVE YOUR PATIENTS THE BEST TECHNOLOGY AVAILABLE

The Intermountain Precision Genomics™ team consists of physicians and researchers from around the world. Together, they study each case individually and explore every possible treatment option.

BETTER TESTING: The ICG100 test detects individual genes with errors within a patient’s DNA, allowing oncologists to better determine treatment options.

BETTER METHODS: Intermountain Precision Genomics™ Core Laboratory is certified with the College of American Pathologists and is authorized under Clinical

WHO IS ELIGIBLE FOR TESTING? The genomics treatment method is currently being used for patients who have late stage cancer and have failed a traditional treatment method.

Laboratory Improvement Amendments to perform high-complexity testing.

BETTER RESULTS: Unlike traditional therapies, our Molecular Tumor Board recommends targeted therapies that identify and target specific gene mutations.

BETTER THERAPIES: Through a simple ordering process, Intermountain Precision Genomics™ can quickly procure targeted treatments for your patient.

6

7

TESTING TIMELINE

1

SAMPLE RECEIVED

The physician’s office is notified when a sample is received. (The physician is also notified after extraction if the sample is not sufficient.)

5

WET LAB

2

PROGRAM BY THE NUMBERS

5-7 days — The physician is notified once sequencing is complete.

Less than 14 day turnaround time

Actionable mutations detected

Molecular Tumor Board meets each week

With you every step of the way

PROCUREMENT (OPTIONAL)

Up to 2 weeks (average) — The patient is sent a medication (if the physician elected to prescribe one).

3

BIOINFORMATICS

4

MOLECULAR TUMOR BOARD

2 days or less — The physician is notified when the report is generated.

8

5 days — The physician is notified that the sample has completed curation and informed of the date for the Molecular Tumor Board.

98% Sensitivity

96% Specific

Regions

Depth of coverage 9

SAMPLE REPORT COMPREHENSIVE, INTERACTIVE FINAL REPORT Intermountain Precision Genomics™ ICG100 is a comprehensive test that uses state-of-the-art next-generation sequencing to find and target individual somatic mutations within cancer tumors.

EMPOWERING TEST ANALYSIS ICG100 is cost effective and offers high sensitivity. From start to finish, the entire ICG100 process averages a 16-day turnaround time. The final report of the ICG100’s comprehensive tumor

PERSONALIZED TESTING

sequence analysis is available online and as a PDF download so that it can be easily printed and shared with the patient.

ICG100 offers a targeted cancer panel that detects 96 genomic alterations commonly associated with solid tumors. The assay looks at whole-exome sequencing instead of just a hotspot mutation region.

IN-DEPTH RESEARCH EXPERT RECOMMENDATIONS

ICG100 identifies actionable and non-actionable mutation types. Click on the alteration to get more information about

The Molecular Tumor Board is an integrated service that is unique to

the gene mutation. Personalized, interpretive treatment plans

ICG100. The collaborative, interdisciplinary board consists of expert scientists and physicians who recommend individual, effective treatment

are then linked with verified, precision cancer medications.

options based on genomic data and clinical relevance. The Molecular Tumor Board ranks the actionable mutations and corresponding suggested drug therapies.

POSSIBLE CLINICAL TRIALS

CONVENIENT DRUG PROCUREMENT

Click on the clinical trial ID number for more details and contact information for each available clinical trial. Report includes all relevant clinical trials by region and clinical significance.

The final report provides the option for one-step ordering of the recommended targeted drugs. Oncologists can make a treatment selection and order precision medications with ease and convenience.

PROVEN METHODOLOGY PRECISION CANCER CARE ICG100 provides superior capability for clinical management through the identification of actionable genes, genomics-driven personalized treatment plans, and precision cancer care.

10

Intermountain Precision Genomics™ ensures a qualitative and highly accurate sequence from the patient’s exome. The process is completed with an in-house bioinformatician and lab director who approve of a cross-validated consensus.

11

N-OF-ONE ONCOLOGY DECISION SUPPORT IN EVERY REPORT

EXPERT CLINICAL INTERPRETATION N-of-One’s Clinical Interpretation defines the effect of tumor alteration(s) detected by Intermountain Health’s ICG100 test, and links them to relevant treatment strategies. The patient-specific therapeutic options are based on the most current scientific and clinical evidence available for each disease gene variant.

N-OF-ONE ADVANTAGES: ONCOLOGY DECISION SUPPORT BASED ON SIGNIFICANT DOMAIN EXPERTISE N-of-One’s team of Ph.D. scientists collaborate with N-of-One’s on-staff oncologists, who are practicing and doing research at major cancer centers in the USA.

PATIENT-SPECIFIC MULTIVARIANT ANALYSIS Optimal decision support in oncology requires

LARGEST SOMATIC KNOWLEDGE BASE

the consideration of all of the individual’s tumor

Tens of thousands of patient cases have been analyzed

alterations in order to understand their full impact on

across more than 800 cancer sub-types, while relying on

each other, and consequently on treatment strategy,

high quality processes and supporting technology.

including combination therapies. Both drug sensitivity and drug resistance may be relevant.

CONSISTENT HIGH QUALITY Leveraging an expert team with oncology domain expertise and a rapidly growing database of patient

SOPHISTICATED CLINICAL TRIAL MATCHING N-of-One delivers biomarker-specific clinical trial

cases, N-of-One is able to produce the most relevant treatment strategies for each patient case.

matching based on the patient’s molecular eligibility, and prioritized by clinical and geographic specificity.

12

13

PUBLISHED ABSTRACTS Precision Medicine to Improve Survival Without Increasing Costs in Advanced Cancer Patients

Implementation of a Precision Cancer Program in an Integrated Health Care System

Journal of Clinical Oncology® — The Official Journal of the American Society of Clinical Oncology®

Journal of Clinical Oncology® — The Official Journal of the American Society of Clinical Oncology®

Background

Background

The advent of Next-Generation Sequencing (NGS), and other diagnostic technologies, has enabled the use of genomic information to guide targeted treatment in cancer patients. The outcomes and costs associated with the implementation of precision cancer medicine have been difficult to generate. Leveraging the advantages of an integrated healthcare system, we have implemented a clinical cancer genomics program to personalize targeted treatment for advanced cancer patients in a community setting. We report a retrospective analysis of the clinical outcomes associated with precision cancer medicine.

Methods

We conducted a matched cohort study of 72 patients from July 2013 to December 2014, with metastatic cancer of diverse subtypes. The outcomes of 36 patients treated with precision cancer medicine were compared to 36 historical control patients who received standard chemotherapy. Study and control patients were matched according to age, gender, histological diagnosis, and number of previous treatment lines. PFS was compared between the two groups using a Cox Proportional Hazard model for survival and accounting for potential confounders. Costs includes ED visits, hospitalizations, NGS costs and costs for targeted or standard therapy.

14

Results

Progression free survival was 22.9 weeks for the treatment group and 12.0 weeks for the historical control group (p = 0.002). Patients receiving precision cancer medicine compared to conventional treatment patients had a hazard ratio of 0.47 (95% confidence interval of 0.29-0.75) when adjusting for age, gender, histological diagnosis and previous treatment lines. Costs per week were $3,204 in the targeted group and $3,501 in the control cohort (p = 0.382).

Conclusions

Precision cancer medicine appears to significantly improve survival for patients with advanced cancer when compared to control patients who received conventional chemotherapy. The additional survival is not associated with increased costs. While the results of this study warrant further investigation in the setting of a prospective randomized control trial, this genomics-based approach appears to be a viable, and perhaps superior, option for patients with advanced or metastatic cancer. Authors: Lincoln Nadauld, S. Burke Van Norman, Gail Fulde, Justin G. McDermott, David

Newman, Allison M. Butler, Brian P. Tudor, Heather Gilbert, Karen Yin Lin, Gary Stone, James M. Ford, Derrick S. Haslem; Intermountain Healthcare, St George, UT; Intermountain Healthcare, Salt Lake City, UT; Stanford University School of Medicine, Stanford, CA e17641, Journal of Clinical Oncology, 2015, Vol 33 (suppl; abstr e17641)

The advent of Next-Generation Sequencing (NGS), and other diagnostic technologies, has enabled the use of genomic information to guide targeted treatment in cancer patients. Barriers to implementation of a precision cancer clinic in a community setting include ability to perform appropriate NGS testing, interpretation of results, and drug procurement. Leveraging the advantages of an integrated healthcare delivery system, we implemented a precision cancer program for advanced cancer patients in a community setting. This program includes NGS testing, interpretation by a multi-institutional Molecular Tumor Board (MTB) and a drug navigation process.

Methods

In July 2013, we began seeing metastatic cancer patients who had failed standard treatments in our precision cancer clinic. Patients with a good performance status and ability to consent were eligible. NGS was performed on fresh or archival tissue and each case was presented at our MTB which consists of experts in oncology and cancer genomics. Recommendations from the MTB were given to the treating physician, who then discussed with the patient. If it was decided to treat with the new agent, a drug navigation specialist worked with payers to obtain the drug, sometimes resulting in a complex appeals process. Patients were monitored for survival outcomes, cost and adverse events.

Results

To date, 243 patients with a variety of tumor types have had NGS performed on their tumor as part of our precision cancer clinic. 188 patients (77%) had actionable mutations. This resulted in a treatment change to the targeted drug in 117 patients (62%). In addition, 38 patients (20%) have targeted options available, but are awaiting disease progression through their current treatment. Our drug navigation system has successfully obtained drugs for 155 patients (82%) through insurance approval, appeals processes or clinical trials.

Conclusions

Although barriers to precision cancer clinics exist, they can be overcome in the community setting through appropriate implementation of NGS, access to a MTB and a drug procurement process. In the era of personalized medicine, this model offers improved access to genomic medicine for advanced cancer patients outside of the academic setting.

Authors: Lincoln Nadauld, Derrick S. Haslem, Gary Stone, Pravin J. Mishra, Sharanya Raghunath,

Jason L. Gillman, David L. Loughmiller, James M. Ford; Intermountain Healthcare, St George, UT; Intermountain Healthcare, St. George, UT; Stanford University School of Medicine, Stanford, CA e17647, Journal of Clinical Oncology, 2015, Vol 33 (suppl; abstr e17647)

15

CLINICAL PATHWAY PATIENT DIAGNOSED WITH STAGE IV CANCER

Doctor orders genomic testing

Patient starts standard therapy Was the standard therapy successful?

Molecular Tumor Board conducts tests and discusses results. Doctors reference report for guidance and consider targeted therapies.

No

Yes

Monitor and consult with Molecular Tumor Board as needed based on patient response to targeted therapy. 16

Begin targeted therapy

Continue standard therapy

Intermountain Precision Genomics incorporates a proven process model within an integrated Healthcare System. This Clinical pathway model is recommended for superior patient outcomes. 17

LABORATORY INFORMATION METHODS

CLIA & CAP CERTIFIED Intermountain Precision Genomics™ Core Laboratory is currently able to accept samples from 48 states and is certified with Clinical

MOLECULAR TUMOR BOARD

Intermountain Precision Genomics™ provides comprehensive tumor profiling for 96 genes that play a role in cancer pathways. The clinical lab operates under strict CLIA-CAP

This integrated service utilizes a collaborative Molecular Tumor Board that consists of subject expert scientists and physicians.

guidelines providing the highest quality of data to ordering physicians. DNA extracted from the patient’s tumor specimen gets sequenced for 96 cancer-related genes which may be

This interdisciplinary tumor board suggests effective treatment options based

altered. These targeted regions are sequenced on Illumina’s MiSeq and NextSeq platforms

on genomics data and clinical relevance. Actionable genomic alterations are

using an in-solution, oligo-capture sequencing method. The panel covers all coding regions

categorized as such, if linked to an approved therapy in the examined tumor.

and the flanking non-coding regions with a mean depth of coverage greater than 300X.

This test can be ordered by oncologists through a simple web-based interface

This test detects all classes of genomic alterations, including insertions and deletions (indels),

where genomic results and the Molecular Tumor Board’s interpretation can be

CLIA specifies quality standards for

structural variants, copy number alterations and single nucleotide polymorphisms.

viewed. Additionally, oncologists can make a treatment selection and order

proficiency testing, patient test management,

This approach is well-suited for formalin-fixed, paraffin-embedded (FFPE) samples.

medications at their convenience.

Laboratory Improvement Amendments (CLIA) and with the College of American Pathologists (CAP).

quality control, personnel qualifications and

GENE LIST SYMBOLS

quality assurance for laboratories performing moderate and/or high complexity tests.

SNPs

Insertions

Deletions

CAP’s laboratory accreditation program is widely recognized as the ‘gold standard’ and has served as a model for various federal, state, and private laboratory accreditation programs throughout the world.

Sensitivity Specificity Mean depth of coverage Turn-around time

98.83% 93.83%

100%

100%

99.64%

98.94% >300X