recent developments in the classification, diagnosis … · recent developments in the...

RECENT DEVELOPMENTS IN THE CLASSIFICATION, DIAGNOSISAND TREATMENT OF CANCER

FCDS ANNUAL CONFERENCE

BOCA RATON, FLORIDA

7/28/2016

STEVEN PEACE, CTR1

OUTLINE

• 2016 Incidence & Mortality Estimates

• AACR Cancer Progress Report

• ASCO The State of Care in America

• NCCN Annual Report

• Explosion of Data / Fragmented Data Sources

• The Cancer Moonshot 2020 Initiative

• New Diagnostic Tools & Techniques

• Next Generation Genomic Sequencing

• Next Generation of Precision Therapies2

2016 ESTIMATES OF NEW CANCER CASES/DEATHS

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American Cancer Society – Cancer Facts & Figures 2016

ANTINEOPLASTIC AGENTS RECENTLY APPROVEDBY CANCER TYPE OR SITE AND DRUG CLASSIFICATION

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WHO CLASSIFICATION OF NEOPLASMS (2012-2016)

• WHO Classification of Tumours of the Urinary System and Male Genital Organs; WHO/IARC Classification of Tumours, 4th Edition, Volume 8 (2016)

• WHO Classification of Tumours of the Central Nervous System; WHO/IARC Classification of Tumours, 4th Edition Revised, Volume 1 (revised 2016)

• WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart; WHO/IARC Classification of Tumours, 4th Edition, Volume 7 (2015)

• WHO Classification of Tumours of Female Reproductive Organs; WHO/IARC Classification of Tumours, 4th Edition, Volume 6 (2014)

• WHO Classification of Tumours of Soft Tissue and Bone; WHO/IARC Classification of Tumours, 4th Edition, Volume 5 (2013)

• WHO Classification of Tumours of the Breast; WHO/IARC Classification of Tumours, 4th Edition, Volume 4 (2012)

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AMERICAN ASSOCIATION FOR CANCER RESEARCH

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AACR Cancer Progress Report 2015

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AACR Cancer Progress Report 2015

AMERICAN SOCIETY OF CLINICAL ONCOLOGY

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Cancer care in the United States remained a mixed picturein 2015. Declining mortality rates, growing numbers ofsurvivors, and exciting progress in treatment were set

against the backdrop of increasingly unsustainable costsand a volatile practice environment.

ASCO – The State of Cancer Care in America 2016

COST

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NATIONAL COMPREHENSIVE CANCER NETWORK

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NCCN Annual Report

NATIONAL COMPREHENSIVE CANCER NETWORK

• NCCN Guidelines – Clinical Practice Guidelines in Oncology

• NCCN Drugs & Biologics Compendium

• NCCN Biomarkers Compendium

• NCCN Oncology Research Program

• NCCN Content in Health Information Technologies

• NCCN Best Practices for Biorepositories, Registries, and Databases

• NCCN Oncology Outcomes Database

• NCCN Patient & Caregiver Resources

• NCCN Guidelines for Patients12

NCCN Annual Report

EXPLOSION OF DATA / FRAGMENTED DATA SOURCES

• Cancer Registry Core Data

• Cancer Registry Enhanced Data

• Biorepository Data & Linkage Results

• Changes in Classification of Neoplasms

• Tumor Genetics and Molecular Biomarkers

• Complex Variety of Antineoplastic Agents

• Targeted Treatment Methods

• Patient Outcomes Data

• Clinical Trials Data 13

CANCER DATA STANDARDS

NCCN Annual Report

THE CANCER MOONSHOT 2020 INITIATIVE

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“For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country

that cures cancer once and for all”

President Barack Obama

State of the Union Address

January 12, 2016


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• 1/13/2016 - During his 2016 State of the Union Address, President Obama called on Vice President Biden to lead a new, national “Moonshot” initiative to eliminate cancer as we know it. Investing in the National Cancer Moonshot

• 2/1/2016 - White House announced $1 billion initiative to jumpstart the work.

• The initiative aims to bring about a decade’s worth of advances in five years, making more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage.

• Pave the Way for Large-Scale Computational Cancer Science with “ExascaleComputing Initiative and the national Strategic Computing Initiative”

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National Cancer Moonshot Initiative


• The Departments of Defense and Veterans Affairs to increase research investments.

• The Vice President’s Exceptional Opportunities in Cancer Research Fund

• 7 Primary Working Groups will manage high-profile research portfolios targeting;

• Prevention and Cancer Vaccine Development

• Early Cancer Detection

• Cancer Immunotherapy and Combination Therapy

• Genomic Analysis of Tumor and Surrounding Cells

• Enhanced Data Sharing

• Oncology Center of Excellence

• Pediatric Cancer 17



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National Cancer Moonshot Initiative and New England Journal of Medicine

THE CANCER MOONSHOT 2020 INITIATIVEThe Blue Ribbon Panel Initial Recommendations (few examples)

• More than 400 ideas have been submitted to NCI’s CancerResearchIdeas.cancer.gov

• Develop ways to make it easier for patients to find and participate in clinical trials.

• Develop a virtual formulary, or library, of cancer drugs that NCI would manage.

• Establish collaborative teams to acquire and characterize pediatric tumor tissues on a much larger scale than is currently done through existing programs

• Target proven cancer prevention strategies for three highly preventable forms of cancer—cervical, colorectal, and lung—among populations with the greatest need

• Implement genetic testing on a wider scale in family members of people with Lynch syndrome and other inherited cancer-associated genetic mutations to determine whether they have inherited the same mutations.

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NEW DIAGNOSTIC TOOLS & TECHNIQUES

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CAP Biomarker Checklist – Lung 2016


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Myriadgenetics.eu


• New Medical Imaging Techniques and Trends in Imaging

• Computed Radiography to Digital Radiography

• Molecular and Genetic Imaging of Cancers & Biomarkers

• Multi-Functional Radiology – Find/Target/Dx/Treat

• Dynamic PET/CT and PET/MRI

• Breast Tomosynthesis (3D Mammography)

• Digital Light Projection Hyperspectral Imaging

• Electromagnetic Acoustic Imaging

• Multimedia Enhanced Radiology Reporting

• Wafer-Scale Mega Microchip

• Dose Reduction24

CR and DR generally deliver a higher

quality image at a lower dose than film

DR can display images in near real time and in most cases has improved dose

efficiency

MedicalImaging.org, DiagnosticImaging.com and American College of Radiology


• Patterns of genetic changes detected in blood samples closely mirror those identified in traditional tumor biopsy. “Liquid Biopsy” provides an accurate snapshot of the genomic landscape of the tumor.

• “Liquid Biopsy” – Biofluids consist of circulating cell-free (ct)DNA and extracellular (ex)RNA from multiple tissues within the body.

• When circulating tumor DNA (ctDNA) was positive for key abnormalities in EGFR, BRAF, KRAS, ALK, RET, and ROS1, the same mutations were reported in tissue 94% to 100% of the time

• ctDNA testing revealed a treatment option for two-thirds of patients tested

• Next Generation Genome Sequencing allows researchers to build new biofluid-based DNA/RNA analytical methods.

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Memorial Sloan Kettering Cancer Center and University of California San Francisco

NEXT GENERATION GENOMIC SEQUENCING

• Next-generation genomic sequencing (NGS), also known as massively parallel sequencing, represents an effective way to capture a large amount of genomic information about a cancer.

• Thanks to advanced computing technology, speed, research collaborations, and cost improvements NGS can now be more readily implemented into a clinical workflow.

• Samples no longer need to be handled differently than standard diagnostic specimens

• Advances have enabled complex genomic data to be derived from peripheral blood.

• The concept of precision medicine goes hand in hand with an understanding of the cancer genome as determined by Next Generation Genomic Sequencing.

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National Cancer Institute Genomic Data Commons


• The Cancer Genome Atlas Project represents the largest effort to systematically characterize the molecular profiles of human cancers. Genetic sequencing has become faster and cheaper.

• The US National Cancer Institute’s Genomic Data Commons (GDC) will bring together the two largest existing cancer datasets - The Cancer Genome Atlas and TARGET – with room to grow

• By profiling tumors—recording in detail the genetic sequence, structure, and differences from healthy cells—they will reveal clues about how to stop them – one huge unified database

• Development of advanced bioinformatics tools for analyzing and visualizing genomic data.

• Evaluation of genome atlas molecular data to predict patient survival.

• Evaluation of genome atlas molecular data and treatment targets to affect survival across types.

• Biomedical significance and clinical relevance of pseudo-genes and RNA editing in cancers.

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• The NCI's Genomic Data Commons (GDC) it is an expandable knowledge network supporting the import and standardization of genomic and clinical data from cancer research programs.

• The GDC provides the cancer research community with a unified data repository that enables data sharing across cancer genomic studies in support of precision medicine.

• The GDC supports several cancer genome programs at the NCI Center for Cancer Genomics (CCG), including The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI).

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• NCI-Molecular Analysis for Therapy Choice or NCI-MATCH precision medicine clinical trial is exploring treating patients based on the molecular profiles of their tumors.

• Analyzes patients’ tumors to determine whether they contain genetic abnormalities for which a targeted drug exists and assigns treatment based on the abnormality.

• Currently there are 24 treatment arms

• Goal: 25% of cancers are rare neoplasms29

NEXT GENERATION OF PRECISION THERAPIES


• NCI-MATCH utilizes advanced DNA sequencing extensively validated across four certified clinical laboratories for high consistency of results.

• NCI-MATCH is designed to be able to detect responses to the inhibition of driver mutations in more than one tumor type.

• The trial has included many more drugs for testing than most other clinical trials and is including even more drugs as additional arms are added.

• Many pharmaceutical companies are collaborating in NCI-MATCH and have also contributed their expertise. 30

National Cancer Institute MATCH Trial

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NCI MATCH – 24 ARMS in Trial to Date

The Pediatric MATCH Trial will begin in late 2016 for pediatric targets

National Cancer Institute MATCH Trial

NEXT GENERATION PRECISION & IMMUNE-BASED THERAPIES

• Neurosurgery at Maryland have genetically programmed a type of common cold virus (Adenovirus Delta-24-RGD) to attack glioblastoma multiforme.

• Targeting Cancer with Genetically Engineered Poliovirus (PVS-RIPO) • PVS-RIPO naturally infects almost all cancer cells – now genetically engineered version

• PVS-RIPO naturally targets and destroys cancer cells from most common cancer types (pancreas, prostate, lung, colon, and many others)

• PVS-RIPO kills cancer cells, but not normal cells, because its ability to grow (and kill) depends on biochemical abnormalities only present in cancer cells

• The target for PVS-RIPO is also glioblastoma multiforme

• University of Pennsylvania using a deactivated HIV virus caused patients with acute lymphoblastic leukemia to go into remission. The T-cells become serial killer cells literally going from one tumor cell to the next to kill them. 32

• Venetoclax Approved for Chronic Lymphocytic Leukemia with 17p deletion• 17p deletion leads to the loss of the tumor-suppressor gene TP53

• 17p deletion tumors have high risk of disease progression with only few years survival

• Venetoclax is the first FDA-approved drug that targets the BCL2 protein in cancer cells

• MyPathway enrolled patients with advanced cancer whose tumors had genetic alterations in any of four specific signaling pathways: HER2, BRAF, EGFR, and Hedgehog. None had a cancer for which the drugs are already approved.

• HER2 alterations – Trastuzumab (Herceptin) and pertuzumab (Perjeta)

• BRAF mutations – Vemurafenib (Zelboraf)

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• Keytruda (pembrolizumab) and Nivolumab(Opdivo) target melanoma immune checkpoint inhibitor genes called PD-1 and PD-L1. Ipilimumab (Yervoy) targets CTLA-4 similarly.

• The interaction between the two genes allows some tumors to escape detection and normal destruction by immune system cells.

• Atezolizumab (Tecentriq) targets bladder tumor microenvironment immune checkpoint inhibitor proteins PD-L1 and PD-1.

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• IMAB362 (claudiximab) targets a specific protein used to form cell membraneBinds to tumor cells then enlists other parts of immune system to attack them –gastric cancer trials

• DLBCL – most common NHL - two new distinct molecular DLBCL subtypes identified which are now being used as treatment targets to interrupt TKI BCR signaling pathways

• GBC DLBCL – activation of GBC pathways

• ABC DLBCL - least curable with current therapy – activates BCR signal pathways

• Ibrutinib (Imbruvica) showing promise in patients with ABC DLBCL – blocks BCR Signaling


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• Targeted Photoimmunotherapy - a novel type of cancer immunotherapy that uses infrared light to activate rapid and selective killing of cancer cells.

• Testing in head and neck cancers which overexpress EGFR.

• Near-infrared photoimmunotherapy uses an antibody–photoabsorber conjugate that binds to cancer cells.

• When near-infrared light is applied, the cells swell and then burst, causing the cancer cell to die.

• Limitation – deep tissue cannot be penetrated without light fiber implant or scope


REFERENCES

• National Cancer Institute – MATCH TRIAL

• The Genome Atlas Project and The NCI Cancer Genomic Data Commons

• The National Cancer Moonshot Initiative – various sources

• Clinical Cancer Advances 2015 - J Clin Oncol 33. © 2015 by American Society of Clinical Oncology

• American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016.

• The State of Cancer Care in America 2016 – American Society of Clinical Oncology

• AACR Cancer Progress Report 2015 – American Association for Cancer Research

• ASCO 2015 Annual Report – American Society of Clinical Oncology

• NCCN 2015 Annual Report – National Comprehensive Cancer Network

• WHO/IARC Classification of Neoplasms Series Updates and Revisions (2012-2016)

• College of American Pathologists – Dr Richard Moldwin – Explosion in Cancer Data: What to do? 37

QUESTIONS

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