Data Driven Treatment

Strategies

Matthew CLARK

Elsevier R&D Solutions

As experts in scientific

domains, industry-standard

taxonomies, and the manual

curation of content, our team

can quickly assess your

business and propose

solutions to address your most

complicated data challenges.

Deep Life Sciences Domain Experience

We integrate, harmonize,

and analyze data across

the pharma lifecycle

E L S E V I E R D A T A

C U S T O M E R D A T A

T H I R D P A R T Y I N F O R M A T I O N

U N P A R A L L E D D O M A I N

E X P E R T I S E

A C C E S S T O A F O U N D A T I O N O F S E M A N T I C A L L Y R I C H C O N T E N T

Elsevier – Continuous Reinvention

01.11.2019

Publications

Reference Databases

Expert curated

ClinicalPath

CarePlans

Amirsys

Extracted Data

Pharmapendium

Reaxys

PathwayStudio

ClinicalPath Research Data

Set

16502019

Decision Support

AI/ML

Personalized

medicine

*non-linear scale

Finding the right treatment - decisions

based on data• Training

• The right diagnosis

• Radiology

• Pathology

• The right treatment

• Standard of care

• Clinical Pathways

• The right drug - personalized

01.11.2019

Elsevier Data Solutions for Research

Data for driving decisions - Sources• Journal publications – from all publishers

• ~ 33 million biomedical articles

• Data, facts, treatments, are extracted from articles

• Effect of individual genome differences (SNP) extracted

• Patents - 128,000 with biological data and chemistry

• Data from partners

• PHR health records and outcomes

• Curated image libraries

• Curated clinical pathways (expert panels)

• FDA/Regulatory submissions01.11.2019

Deep Reading to Extract Facts

01.11.2019

4M full-text articles

29M abstracts

53.2M facts supported by

18M sentences

Q356R and S15121 are BRCA1 variants that may be associated with breast cancer

subject verb object

Clinical Pathway

01.11.2019

• A clinical pathway, also known as care pathway

or care map, is used to manage and standardize

treatment

• Pathways developed with major institutions

like Sloan Kettering or MD Anderson can

help others to elevate the standard of care to

that of those institutions

• Includes diagnostics/tumor expression data

• Allows personalized information to direct

treatment

Standardized Treatment Decision Trees

• From medical

concensus

• Outcome

analysis

• Panels of

Experts

• Approved by

Payers as

standard of care

01.11.2019

Diagnostics and

sequencing should

become standard

pathway

Issue: Drug Efficacy Varies by Patient• Pharmacogenomics (PGx), a substantial component of “personalized medicine”, seeks to

understand each individual's genetic composition to optimize drug therapy

01.11.2019 Ge Zhang Daniel W.Nebert

https://doi.org/10.1016/j.pharmthera.2017.02.036

Classes of drugs with

recognized PGx on label –

Efficacy known to be related

to specific genomic traits

Effect of Metabolism. Tale of Two Patients

01.11.2019

different exposure –

different response

AUC

AUC

CYP

Binding site

01.11.2019

Natalia Mast et al. J. Biol. Chem.

2014;289:3529-3538

CYP46A1 has a complex binding

site, any mutation can affect

rates of metabolism

One of thousands of CYP

Enzymes that are present in

humans

Levels of each can be personal

and affected by diet, disease and

other factors

Efavirenz response

01.11.2019

Case Study For Personalized Treatment

based on Tumor Expression• Collaboration with Personalized Hematology/Oncology of Wake Forest

• Dr. Anton Yuryev, Elsevier

• Used biological pathway data extracted from literature

• Analyzed expression levels and matched to precise pathways of tumor

• Prioritized drugs to treat the tumor

• Dr. Francisco Castillos, Treating Physician

• Chose surgical treatments

• Chose drug therapy based on tumor expression

01.11.2019

Patient Case Study

▪ 66 year old Caucasian female diagnosed with moderate to

poorly differentiated hepatocellular carcinoma with

associated necrosis

▪ Resection of hepatocellular carcinoma involving

the ascending colon in the right lateral abdominal wall,

segments 5 and 6 from the liver and 11 benign lymph

nodes

▪ Core biopsies of liver tumor as well as some of the normal

liver parenchymal cells were sent for gene expression

profile analysis.

01.11.2019

01.11.2019

Dominant signal transduction pathways through which the

hepatocellular carcinoma proliferate is through the Raf- Ras-MEK-Map

kinase pathway.

Sorafenib is

known to inhibit

this pathway

Pathways created

by Deep Reading

matched with data

from tumor

expression

Data Driven Treatment• Patient received Sorafenib 400 mg twice a day at least six months

• Resection of residual disease with gene expression profile using mesenteric lymph node material

from small bowel

• Patient started in randomized in the clinical trial (ClinicalTrials.gov Identifier: NCT01075113)

looking at combinations of molecular targeted therapies inducing apoptosis (Vorinostat) in

addition to the dominant pathway, which were blocked by Sorafenib: EGFR-Ras-Raf- MEK-

Map kinase-ERK pathway.

01.11.2019

Treatment Results

01.11.2019

Before treatment

PET/Scan-July, 2013

After resection and Sorafenib 400 mg

twice a day (six months)-PET/ScanAfter NCT01075113 clinical trial Sorafenib plus

Vorinostat

Massey Cancer Center, Virginia, June 2014-

PET/Scan

Conclusions

• Elsevier is collecting the data, extracting facts, building consensus for

data driven medical care

• Using data allowed medical team to choose the best treatment for this

particular case

• The drugs specifically affected the biological pathways of the specific tumor

• In this case the outcome was positive

• Use of gene expression and diagnostics should be the standad-of-care for

oncology

• Elsevier are committed to helping physicians make the best possible data-driven decisions

for the health of their patients

01.11.2019

Acknowledgements

• Dr Anton Yuryev

• Dr Maria Shkrob

• Dr Frederik van den Broek

• Dr Jabe Wilson

• Dr Eric Gilbert

• Dr Toshikazu Dewa

• Dr Helena Deus

• Timothy Hoctor

01.11.2019