Creating a Precision Healthcare System: Opportunities and Challenges

Creating a Precision Healthcare System:
Opportunities and Challenges
Session #PM3, February 19, 2017

Thomas D Brown, MD, MBA, Executive Director, Swedish Cancer Institute (SCI)
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Speaker Introduction
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Thomas D Brown, MD, MBA

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Executive Director, Swedish Cancer Institute (SCI)
Co-Chair PSJH Personalized Medicine Program
Co-Chair PSJH Cancer Leadership Council
Seattle, Was ... See more

ington

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Disclosures
Consulting
GenomiCare, Inc. – Member, Scientific Advisory Board
Jiahui Holding Co., Ltd – Lead Clinical Advisor
Speaker’s Bureau
Novartis Pharmaceuticals Corporation
Stock
GenomiCare, Inc.

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Agenda
• About Providence St. Joseph Health (PSJH)
• PSJH Personalized Medicine Program (PMP) Overview
– PSJH (SCI) Personalized Medicine Research Program
– PSJH PMP IT Platforms & Clinical Trials Matching
– PSJH PMP Initiatives

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Learning Objectives
• Summarize the implementation of a successful enterprise-wide precision
medicine and research program
• Describe the challenges faced in matching a large population of patients to
clinical trials
• Explain how automated clinical trial matching was implemented through an
innovative IT solution

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Start Presentation Slides Here
60-Minute Lecture
• The speaker must provide a 45-50 minute PowerPoint presentation
(approx. 25-30 slides). Please do not exceed this time limit.
• Leave 10-15 minutes at the end for Q&A

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Providence St. Joseph Health Overview

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PSJH Personalized Medicine Program (PMP)
Program Vision and Goal
• Vision: Create an enterprise wide genomics and personalized
medicine program to best serve our patients and support our
institutes
• Goal: Leverage the knowledge of existing programs within PSJH
to create a nationally recognized clinical and research genomics
program

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PSJH Genomics Focus Groups
Co-Chairs: Thomas Brown, MD, MBA & Walter Urba, MD, PhD
FOCUS GROUPS

LEADS

PURPOSE/PRIORITIES

Bioinformatics

Carlo Bifulco, MD
Paul Tittel

Genomics data storage/cloud-based bioinformatics analysis pipeline
and clinical data integration

Registry/Repository

Charles Drescher, MD
Ora Gordon MD, MS

System wide registry/consent template with networked biorepositories

Laboratory Specifications

Carlo Bifulco, MD
Anna Berry, MD

Alignment and determination of genomics services, platforms, policies
and standards

Clinical Applications

Philip Gold, MD
Karen Appelbaum

Molecular tumor board, patient engagement center integration into
PH&S genomics initiative, and education components

Research

John Pagel, MD, PhD
Rom Leidner, MD

Registry protocol and resource inventory, governance of data usage

Business & Logistics

Nancy Frisco
Jim Yates

Development of business plan/pro-forma and budget
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Key Components – PSJH PMP
•
•
•
•
•
•
•

Patient Engagement Center
300~ Gene Alteration Panel
IRB Approved Registry Trial
Implementation of Bioinformatics Platforms (e.g. Syapse)
Regional Molecular Tumor Boards
Bio-repository Platform
De-identified data sharing (OPeN)
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Swedish Cancer Institute Personalized Medicine
“Double Meaning”
Clinical practice at the SCI is predicated on a research driven, evidence-based,
multi-disciplinary, multi-professional, disease site oriented, patient-centered care
model, in the context of Personalized Medicine. Personalized Medicine in this
context focuses on two meanings:
1. Caring for the whole patient, to include addressing patient and family
socioeconomic, psychological, environmental, and other supportive care
needs;
2. Utilizing molecular (gene, protein, epi-genetic) information from the
patient or their tumor to address cancer risk, prevention, screening, early
and accurate diagnosis, treatment of disease, and survivorship.
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SCI (PSJH) Personalized Medicine Program Progress
2014 Mar
PMP Panel 1st Edition
(68 gene panel)

2015 Jan
Molecular Tumor Board
Launch

2014 Sep
Personalized Medicine
Research Program Protocol
(IRB approved)

2015 Nov
PMP IT Platform
(Syapse) Launch

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2016 Mar
Innovative Therapeutics
Unit (Early Phase Clinical
Trials Unit) Open

2016 Nov
PMP Panel 2nd Edition
Portland (4Q, 2016)
and Seattle (2Q, 2017)

PSJH PMP Panel – 2nd Edition

• Expansion to 300+ genes (Portland / 4Q, 2016 and Seattle / 2Q, 2017)
• Published literature on cancer genomics

• TCGA data for major cancer types
• Specialized set of genes for hematologic malignancies
• Treatment and pathway-based strategies

• Mutation types to be covered:
• Point mutations, small insertions and deletions
• Copy number variations
• Common fusions in solid tumors
• Most of the known fusions in leukemia and lymphoma
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SCI PMRP: Eligibility Criteria
Inclusion Criteria
•

Patients with active malignancies or selected pre-malignant conditions to include:
myelodysplastic syndromes (MDS), actinic keratosis, Barrett’s esophagus, cervical
dysplasia, colonic polyps, lung metaplasia, and oral leukoplakia

•

18 years of age, or older

•

ECOG performance status of 0 to 2

•

A candidate for anti-cancer therapy

•

Life expectancy of at least three months

•

Measurable or evaluable disease is not required; e.g. patients in the adjuvant
setting may be enrolled, if clinically appropriate
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SCI PMRP: Eligibility Criteria (cont’d)
• Prior malignancy or multiple current malignancies allowed
• Patients who previously had gene sequencing are allowed
• All patients must be informed of the investigational nature of this study, and
must give written informed consent, in accordance with institutional and
federal guidelines
Exclusion Criteria
• Patients who are not able to understand and consent for themselves to the
PMRP
• Patients who do not have sufficient tissue available for the PMP Panel
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SCI PMRP: Recruitment/Enrollment
• Enrollment: 877 patients (as of January 9th, 2017); initial focus on solid tumors

• Locations: SHS First Hill, Cherry Hill, Edmonds, Ballard, Issaquah; Swedish
Neurosciences Institute (SNI). To expand to include Providence Olympia,
Portland and Everett
• Insurance Status: No restrictions
• Cost to Participate in PMRP: None (PMP Panel ordered by provider, and billed
based on “medical necessity”)
• Language: Consent form in English, Vietnamese, Korean, Japanese, Chinese
(Mandarin & Cantonese), Russian and Spanish
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SCI PMRP Workflow
Testing

Patient receives gene
sequencing test (based
on medical necessity)

Enrollment

Patient signs
consent

Follow-up

Update

Patient is followed, at least
Provider and
annually, to review disease
patient receive
status and to identify need for updated reports
clinical interpretation update

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PSJH PMP – Informatics Platform
Clinical Interpretation

(e.g. annotation, therapeutic
options, literatures)

External Labs

Molecular
Pathology

Genomic Data & Tools

(e.g. genetic &
genomic testing)

(e.g. TCGA - Human Genome Project)

Portland

State/ National
Registries
Disease Site Registries
(Research)

Clinical Trials.Gov

Clinical & Genomic
Medicine Platform

Synoptic
Pathology

Collect, manage, integrate, visualize, analyze
& share

Providence / Swedish

Clinical Trials
Management System

Enterprise Data Warehouse

Providence Research and
Clinical Trials Website
Existing Platforms

Electronic Medical Record

2017 ~ Platforms
Existing Interface

Providence & Swedish
Cancer Registries

2017 ~ Interface

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PSJH Syapse: Clinical History

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PSJH Syapse: Lab Results

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PSJH Syapse: PMP Panel Results

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PSJH Syapse: PMP Panel Results (Cont’d)

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PSJH Syapse: Similar Patients

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Clinical Trials – Challenges in the Era of Personalized Medicine
Population Level
- Assess clinical trial feasibility in a given population
- Develop agile research infrastructure to accommodate evolving clinical
trials network/design
- Screen and track status of every patient for clinical trial eligibility
- Provide access to all eligible patients in diverse populations

Patient Level
- Identify, integrate and prioritize clinical trial options available within the
system, regionally and nationally, at point of care
- Screen patients against numerous and complex eligibility criteria
- Support patient education and engagement
- Keep treatment options updated throughout continuum of care
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PSJH Syapse: Clinical Trials Guidance

Clinical trials rules engine

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NGS reports

Clinical Trials Matching
Dynamic matching, with results at point-of-care

Current
Future
Patient

Age + Gender

Syapse software automates key parts of workflow:
1. Aggregation of structured clinical & molecular data
2. Structured trial eligibility criteria for high-value data elements
3. Trials matching rules engine – runs nightly to identify
provisional matches across all patients & all trials
4. Clinical trials dashboard for research coordinators & care
team
5. Clinical trial eligibility assessment form in Syapse – prepopulated with patient data
6. Clinical trials feasibility assessment support – advanced query
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Diagnosis Codes
ICD-9 / ICD-10/PMRP

Cancer
Site + Stage + Histopathology

•

Medications

PMRP Staging
Epic Staging
• Cancer Registry
• Breast Registry

Surgery

Lab Results

Radiation Therapy

Hormone Receptors

Performance Status
ECOG score

Toxicity

Clinical trials rules engine
- Study Feasibility
- Screening

•

ER, PR, HER2

Gene Alternations
68-gene NGS

Clinical Trials Matching
Research coordinator dashboard listing provisional trial matches

Show list of patients who have matches and an encounter within next 7 days

Matched trial

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Clinical Trials Matching
Eligibility assessment form with pre-populated clinical data
Structured eligibility criteria

Automatically populated with
relevant patient data from
EHR & other sources

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Clinical Trials Matching

Interface for defining structured criteria for automated pre-screening

Structured eligibility criteria

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Clinical Trials Matching

Early experiences at Swedish Cancer Institute
Swedish Cancer Institute Clinical Trials
• 250 active/enrolling trials
101 active/enrolling therapeutic cancer trials are in Syapse
• 35 trials in Syapse have genomic/biomarker (e.g. hormone receptor) eligibility rules

• 45 trials “published” to active patient matching. 56 trials are not used for clinical trials
matching (e.g. study closed, study not yet opened, study being configured/tested and
used for clinical trials feasibility assessment)
• 40% (~9,000) of SCI patients seen in 2016 have been provisionally matched to at least
one trial in Syapse
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As of Jan 5th, 2017

SCI Molecular Tumor Board
o Co-chairs: Anna Berry, MD; John Pagel, MD, PhD; and Charles Drescher, MD

o Purpose: multidisciplinary case review focused on clinically relevant gene
alterations and associated molecular pathways, with aim of facilitating
patient management decisions
o Conference Structure:

• Average 3-4 cases including follow-up cases
• Cases submitted by physicians and selected by Dr. Berry
• Special sessions (e.g. implications for germline genetic testing)

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Molecular Tumor Board Case – 4/6/15
History:
•

60 yo man, presented in May of 2014 with hemoptysis. He had intermittent fevers
and was treated with antibiotics with a 5 kg weight loss. Smoking history of 10
pack-years, but quit 10 years ago. CT scan showed an 8.8 x 9.6 cm mass in the
right upper lobe (RUL) of the lung, occluding the RUL bronchus and invading the
adjacent mediastinum with enlarged regional lymph nodes.

•

The tumor was resected in June, 2014, along with a separate 1.2 cm nodule in the
RUL adjacent to the main mass. The tumor was staged as pT3, pN0, M0 (IIB).

•

Chemotherapy was offered and declined. He had an extensive local recurrence in
the chest and eventually did start chemotherapy in November, 2014. His disease
has remained stable since, and there is no evidence of distant metastases.

•

Prior Treatment: Chemotherapy (Cisplatin + Paclitaxel, and Cisplatin +
Gemcitabine)
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Molecular Tumor Board Case – 4/6/15

Tissue Tested: Pleural
metastasis and primary
tumor

• Needle biopsy of his RUL mass showed a poorly differentiated squamous cell
carcinoma.
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Molecular Tumor Board Case – 4/6/15
Aberrations:
• PIK3CA-E545K (detected only in
primary tumor)
• PTEN-D162fs*6

Source: Nikiforov Y & Nikiforova MN, Nature Reviews Endocrinology 2011
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Molecular Tumor Board Case – 4/6/15
Significantly mutated genes in lung SQCC

Source: PS Hammerman et al. Nature 000, 1-7 (2012) doi:10.1038/nature11404
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Molecular Tumor Board Case – 4/6/15
• Possible Therapies:
• Everolimus
• Temsirolimus
• Possible Clinical Trials:
•

NCT01226316: Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of
AZD5363 in Different Treatment Schedules (AstraZeneca, OR, CA, and 8 other US locations)

•

NCT01347866: Clinical Study Of PI3K/mTOR Inhibitors in Combination with an Oral MEK
Inhibitor or Irinotecan, in Patients with Advanced Cancer (Pfizer, CA, CO, SC)

•

NCT02260661: Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835
in Patients with Advanced Solid Tumors (AstraZeneca, CO, TN)

•

NCT01827348: NCI-MPACT: Molecular Profiling-Based Assignment of Cancer Therapy for
Patients With Advanced Solid Tumors (NCI, MD)
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FDA-Approved Drugs with a Companion Diagnostic
Drug
Imatinib, Dasatinib, Nilotinib,
Bosutinib

Disease

DNA mutation

Chronic myelogenous leukemia BCR-ABL1 fusion

Action
Indication for therapy
Only indicated for T315I
mutations

Melanoma
Melanoma
Lung cancer

BCR-ABL1 fusion
T315I resistance mutation
EGFR
Exon 19 deletions
L858R
BRAF V600E
BRAF V600E/K
ALK gene fusions

Cetuximab, Panitumumab

Colon cancer

KRAS codon 12, 13

Contraindication to therapy

Olaparib

Ovarian cancer

BRCA1 and BRCA2 mutations

Indication for therapy

Osimertinib

Non-small cell lung cancer

EGFR mutation, T790M

Indication for therapy

Venetoclax

Chronic Lymphocytic leukemia

Deletion 17p-

Indication for therapy

Ponatinib

Chronic myelogenous leukemia

Erlotinib, Afatinib,
Gefitinib

Lung adenocarcinoma

Vemurafenib, Dabrafenib
Tramatenib
Crizotinib

Indication for therapy
Indication for therapy
Indication for therapy
Indication for therapy

Galan J, Van Allen E. Genome Medicine (2015) 7:80.
37 U.S. Food & Drug Administration website (Oct, 2016)

PSJH Personalized medicine Program (PMP)
Program Vision and Goal

2018
2017

2016

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Data sharing through Oncology Precision Network
(OPeN)

•

Founding Members: Intermountain Healthcare, Providence St. Joseph Health, and Stanford Cancer Center

•

Goal: to create a big data resource for clinical care and research using de-identified data

•

Data shared: genetic variants, tumor type/site, tumor stage, histology, tumor biomarkers, recommended
and actual drug treatment, clinical outcomes, ethnicity/race, age and gender of the patient
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TP53 gain of function (GOF) mutations identified by tumor sequencing
performed in the context of a community based Personalized Medicine
Cancer Program
C. W. Drescher1, A. B. Berry1,2, D. J. Beatty1, D. Xu2, X. Liu1, M. Zhang2, K. Keith2, J. D. Scanlan3, J. M. Pagel1, P. J. Gold1, D. Markowitz1, T. L. Benkers4, C.
Bonham1, M. Tameishi1, T. D. Brown1. 1Swedish Cancer Institute, Swedish Cancer Institute. 2CellNetix Pathology and Laboratories, Molecular Pathology.
3Swedish Medical Center, The Swedish Center for Research and Innovation. 4Swedish Neuroscience Institute, Ben & Catherine Ivy Center. EORTC-NCIAACR Molecular Targets and Cancer Therapeutics Symposium, Nov, 2016.

•

Overall 47 pts (10%) of 468 pts were identified as having GOF mutations.

•

The frequency of GOF mutations varied by disease site (X2 = 37.8, p<0.001); these results were driven largely by the absence of GOF
mutations in patients with breast cancer. GOF mutations in decreasing frequency were: R273C, H or L (n= 18), R175H (n=15), R248W or Q
(n=13) and P151S (n=1).

•

Three of the four R273L occurred in patients with NSCLC, and accounted for 60% of GOF mutations in NSCLC pts.
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SCI PMRP Team
Principal
Investigator

Thomas D
Brown, MD,
MBA

Co-Principal
Investigator

Philip J
Gold, MD

Co-Principal
Investigator

Co-Principal
Investigator

Charles W
Drescher,
MD

Anna
Berry, MD
Alexander, Shlece
Beatty, David
Brindle, Madeleine
Case, Andy
Grevstad, Patra
Iriarte, Desiree
Kaneko, John
Liu, Xiaoyu
Donielle O'Connor
Summers, Lauren
Tameishi, Mariko
Tittel, Paul
Varghis, Nina
Yates, Jim

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Co-Principal
Investigator

John Pagel,
MD, PhD

Technical
Expert

Danbin Xu,
MD, PhD

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Questions
Thomas D Brown, MD, MBA
Executive Director, Swedish Cancer Institute (SCI)
Co-Chair PSJH Personalized Medicine Program
Co-Chair PSJH Cancer Leadership Council
Seattle, Washington
Email: Thomas.Brown@Swedish.org

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