AACR Report BackAACR Report Back

May 29, 2014May 29, 2014

Annie Ellis

Ovarian Cancer Survivor Advocate

2014 AACR Report Back

� Highlights from 2014 AACR Annual Meeting

� AACR Scientist↔Survivor Program

◦ 5x5 Survey and Poster

� Strategies for Dealing with Research Information

Annie Ellis

� Ovarian and Breast Cancer Survivor

� SHARE Helpline Peer

� NY Presbyterian Woman to Woman

� OCRF clinical trials video, symposium

� OCNA research advocate, committees

� CDMRP OCRP Integration Panel

� Founded: 1907 by a group of 11 physicians and scientists interested in research, "to further the investigation and spread the knowledge of cancer."

� Mission: To prevent and cure cancer through research, education, communication, and collaboration.

� The AACR fosters research in cancer and related biomedical science; accelerates the dissemination of new research findings among scientists and others dedicated to the conquest of cancer; promotes science education and training; and advances the understanding of cancer etiology, prevention, diagnosis, and treatment throughout the world.

� www.AACR.org

Targets and Targeted TherapiesTargets and Targeted Therapies

� Opening Plenary: Harnessing Breakthroughs, Targeting Cures

� Recent advances in massively parallel sequencing have made possible high throughput analysis of tumor samples bringing targeted treatment strategies and individualized medicine

� Genomic basis for the heterogeneity of outcomes

� Biomarkers driving trials

� Personalized Medicine: The right individual, the right care, the right time and the right place

Final Results PALOMAFinal Results PALOMA--1; TRIO1; TRIO--1818

� Presentation Abstracthttp://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=113bcbb9-585d-4939-b5de-99e11e302ef2&cKey=54090e4a-2f25-4594-83b3-37e21e120e6b&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� AACR in the News Article: Palbociclib Shows Promising Results in Patients With Hormone Receptor-positive Metastatic Breast Cancerhttp://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3335

� Phase II Ovarian Cancer palbociclib trial:http://www.cancer.gov/clinicaltrials/search/view?cdrid=727128&version=HealthProfessional&protocolsearchid=6378902

Two Faces of p53Two Faces of p53Tumor Suppressor and Tumor Suppressor and OncogeneOncogene

� Presentation Abstracthttp://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=3404&sKey=113bcbb9-585d-4939-b5de-99e11e302ef2&cKey=88d9c548-3f51-46c2-9da9-7faafccbc7f3&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� Article in Genes & Development: P53: puzzle and paradigm (Ko and Prives)http://genesdev.cshlp.org/content/10/9/1054.full.pdf+html

Targets and Targeted TherapiesTargets and Targeted Therapies

Challenges:

�Drivers and Passengers

�Heterogeneity within tumors

�Moving targets: DNA methylation, transcription factors, dedifferentiation

�Biomarker reproducibility

�Incidentalomes

� Vanderbilt

� My Cancer Genome is a personalized cancer medicine knowledge resource for physicians, patients, caregivers and researchers.

� My Cancer Genome gives up-to-date information on what mutations make cancers grow and related therapeutic implications, including available clinical trials.

� www.MyCancerGenome.org

� MDAnderson

� Functional proteomics represents a powerful approach to rapidly improve understanding the pathophysiology and therapy of cancer.

� Currently contains 4,495 tumor samples from (i) TCGA tumor tissue sample sets; (ii) independent tumor tissue sample set; and (iii) >500 cell-line samples.

� Provides a unique opportunity to validate the findings from TCGA data and identify model cell lines for functional

investigation.

� http://bioinformatics.mdanderson.org/main/TCPA:Overview

ImmunotherapyImmunotherapy

� Phase I and II: Dramatic and durable responses of anti-PD-1 (MK-3475) in heavily pre-treated melanoma and non-small cell lung cancers expressing high levels of PD-L1. PD-1 on T cells attaches to PD-L1 on tumors, activating PD-1 checkpoint (brake).

� Abstractshttp://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=1a1f4fbb-a45d-407f-861e-75f8d79db782&cKey=9c9fbd12-e5c1-43c0-9064-87f04cb12932&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=1a1f4fbb-a45d-407f-861e-75f8d79db782&cKey=875f683f-04fe-450a-a9cb-f51cac5436b8&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� AACR in the News Article: Biomarker Identifies Melanoma Patients Who May Respond to Immunotherapy MK-3475http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=3307

ImmunotherapyImmunotherapy

� Adoptive T-Cell Transfer Abstracthttp://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6770f171-dc66-40bb-91ce-24c030599343&cKey=7d724368-46c7-47b8-8050-087713c49aef&mKey=6ffe1446-a164-476a-92e7-c26446874d93http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8092f9c1-a235-4394-80fa-127f695cb77f&cKey=b6493065-dcbb-40e8-8e6b-1a89f4321202&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� Clinical Cancer Research article: Adoptive Transfer of MART-1 T-Cell Receptor Transgenic Lymphocytes and Dendritic Cell Vaccination in Patients with Metastatic Melanomahttp://clincancerres.aacrjournals.org/content/20/9/2457.abstract

� Anti-CD74 Abstracthttp://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=1869083e-dcfc-4125-a25f-0d5faf5b47be&cKey=706bae4d-b593-4f94-9c36-80a3930c90c3&mKey=6ffe1446-a164-476a-92e7-c26446874d93

� Ongoing research: find biomarkers to identify patients most likely to respond to specific immunotherapies and exploring ways to stimulate the immune system.

Repurposing Repurposing MetforminMetformin and Aspirin for and Aspirin for

Cancer Prevention and TreatmentCancer Prevention and Treatment

� Epidemiologic and animal studies have associated metforminand aspirin with a reduction risk of several cancers.

� Retrospective analyses have correlated metformin with increased survival in ovarian cancer.

� Research is ongoing to understand how metformin and aspirin may work to reduce risk and/or influence survival

� Ongoing metformin clinical trials in ovarian cancer: http://clinicaltrials.gov/show/NCT01579812; http://clinicaltrials.gov/show/NCT02050009

Current Concepts in Organ Site ResearchCurrent Concepts in Organ Site Research

——A Systems Approach to Ovarian CancerA Systems Approach to Ovarian Cancer

� Ronny Drapkin, Dana-Farber: Insights into the origins of ovarian cancer

◦ P53: earliest genetic mutation in HGS

◦ Telomere shortening, CNA (copy number alterations), HR dysfunction (Homologous Recombination)

◦ Tumor Avatar Programhttp://championsoncology.com/wp-content/uploads/2013/11/P.-Malaney-et-al-One-mouse-one-patient-paradigm-New-avatars-of-personalized-cancer-therapy-Cancer-Lett-2013.pdf

◦ Mouse surgery study: FT no STC (serous tubal carcinoma), ovary had STC (Theory: even if ovary is not origin, plays a role in seed and spread)

� James Brenton, Cambridge: Detection of Circulating Tumor DNA (ctDNA) and possible use as a biomarker for detection and monitoring treatment (http://www.ncbi.nlm.nih.gov/pubmed/22649089)

� Sandra Orsulic, Cedars-Sinai: Exploration in mice of the metabolic pathways (Succinate Dehydrogenase) involved with ovarian cancer

� Gordon Mills, MDAnderson: Study of potential targets: P13K, PTEN

Consortium efforts to discover ovarian Consortium efforts to discover ovarian

cancer risk variantscancer risk variants

� Thomas Sellers, Moffitt

� Genetic Associations and Mechanisms in Oncology (GAME-ON): A Network of Consortia for Post-Genome Wide Association (Post-GWA) Researchhttp://epi.grants.cancer.gov/gameon/

� Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)

� Studying SNPs (single-nucleotide polymorphism) and CNVs (copy number variations)

� 10% life-time risk for consideration of actionable interventions

Interesting PostersInteresting Posters

� Emiliano Cocco (Yale): Fluorescence imaging using Clostridium Perfringens Enterotoxin carboxi terminal fragment (c-CPE) to target metastatic chemotherapy-resistant human ovarian cancer in xenograft mice

� Luke Peppone (University of Rochester): The Effect of YOCAS©® Yoga on Prescription Sleep Medication and OTC Sleep Medication Usage in Cancer survivors with Impaired Sleep Quality

� Anees ChagPar (Yale): Physical activity is associated with improved QoL in cancer survivors: A population-based analysis

� Julia Parrish-Novak (Blace Bioscience): Tumor Paint™technology detects naturally occurring solid tumors in dogs

Drug ResistanceDrug Resistance

� Targeted therapies have produced dramatic regressions, but responses are often short-lived because resistant cancer cells arise.

� Researchers are studying mathematical theories and the mechanics of how cancers evolve and develop resistance to treatments so strategies to overcome resistance can be constructed.

� Evolutionary dynamics of cancer in response to targeted therapy (Martin Nowak, Harvard)Researchers used a mathematical model describing the evolutionary dynamics of lesions in response to treatment to study pancreatic, colorectal, and melanoma cancer patients with metastatic disease. Dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs.

� SSP SIS Overcoming Drug Resistance (Charles Sawyers, MSKCC) Effective strategies to overcome resistance are within reach, but widespread sharing of genomic and clinical data is required to make progress. To gain understanding, it is important that tumor samples are collected both before and after treatments.

Drowning in Big DataDrowning in Big Data� The tools to uncover the genomic information needed for personalized medicine have generated a “data tsunami”

� Velocity, Variety, Volume

� Patient data expected to exceed 28 Petabytes (1 quadrillion bytes) by the end of 2014

� Collaboration across institutions and disciplines is needed to turn the massive amount of data into usable information and knowledge to bring effective personalized medicine to patients more quickly

� Data►Information►Knowledge/Evidence

What Is Research Advocacy?

� Research advocacy brings a non-scientific viewpointto the research process and incorporates the collective patient perspective into research, making scientific and medical advances more timely and effective for people with cancer.

� A collective patient perspective is created when the advocate has knowledge of others’ disease experiences and conveys this collective patient perspective rather than their singular experience.

� Research advocates support well-designed studies and help disseminate results that lead to new and better methods to prevent, detect, and treat cancer.

NCI Office of Advocacy Relations

AACR Scientist↔Survivor Program

� The AACR Scientist↔Survivor Program is designed to build enduring partnerships among the leaders of the scientific and cancer survivor and patient advocacy communities worldwide.

� The program exposes advocates to special lay-language lectures, small group discussions and other interactions that provide a solid background in cancer research.

� AACR Annual Meeting 2015: April 18-22, Philadelphia, PA

� http://www.aacr.org/home/survivors--advocates/scientistharr;survivor-program.aspx

AACR Scientist↔Survivor Program

Before the meeting:

�Submit application

�Recommended reading

�Poster

During the meeting:

�Attend SSP sessions and general sessions

�Present poster

�Working group challenge question

�Connect with researchers and advocates

After the meeting:

�Disseminate information

AACR SSP Special Interest Sessions

� Personalized Medicine

� Advances in Immunotherapy

� The Role of Big DataVideo: http://www.youtube.com/watch?v=_sZSWuRY3vk

� The Biomechanics of Cancer

� Night at the Lab, Peter Kuhn Laboratory at Scripps

◦ Circulating Tumor Cells (CTCs)

◦ Ovarian cancer being studied

� Cancer Action Alliance

◦ URGENT: only 6-8% of grant submissions are funded

◦ Support NIH and hold accountable

◦ AACR Hill Days; Rally for Medical Research

◦ Sign up for alerts: AACR Cancer Action Alliance and Cancer Policy Monitor (http://www.aacr.org/home/public--media/science-policy--government-affairs/advocacy-tools/aacr-cancer-action-alliance.aspx)

AACR Scientist↔Survivor Program

� SSP participants were encouraged to:

◦ Embrace the complexity of cancers

◦ Learn about the evolutionary dynamics of cancers

◦ Consider a systems approach to understanding and treating cancers

� Cancer is a complex adaptive system

◦ The Whole is more and different than the sum of the parts

◦ Cancer occurs in context

AACR SSP Poster: 5x5 SurveyAACR SSP Poster: 5x5 Survey

Navigating Uncharted Waters: Exploring the Resources Patients Use to Manage Long-Term Recurrent Ovarian Cancer

� METHODS: A 30-question online survey was offered to ovarian cancer survivors who have had 5 or more lines of treatment or managed persistent or recurrent disease for 5 or more years.

� RESULTS: 25 respondents provided information about their experiences managing ovarian cancer, including comfort level with participation in treatment decision-making, amount of time spent discussing and researching new treatment options, sources of information and clinical trial participation.

� 2+CLTR SUBGROUP: ◦ Most time researching options◦ 5/6 BRCA+◦ 3/6 Rely most on other survivors

� CONCLUSIONS: Women managing persistent or recurrent ovarian cancer long-term are comfortable participating in treatment selection, spend a great deal of time researching their options and are using many resources to gain knowledge, including each other and materials used by medical professionals. More research is needed to improve outcomes and quality of life for all women diagnosed with ovarian cancer, including those who are able to manage persistent or recurrent ovarian cancer long-term.

Strategies for Dealing with Research Strategies for Dealing with Research

Information OverloadInformation Overload

Oxfordjournals.org

Treatment Decision-making: Consider the Options

Prioritizing Research: Consider More Than Headlines

Prevention vs. Risk ReductionPrevention vs. Risk Reduction

� Understanding Absolute Risk Reduction Versus Relative Risk Reduction (http://www.breastcancerdeadline2020.org)

◦ Let's say the risk of your cancer coming back is 4%. If you taketreatment X, the risk of your cancer coming back is 3%. The difference between 4% and 3% is 1% (4% - 3% = 1%). The 1% decrease in risk is called "absolute risk reduction."

◦ However, your doctor might talk about relative risk reduction instead. He or she might say that your risk will be reduced by 25% if you take treatment X. This is because 1% is 25% of 4% (1% - (3%/4%) = 25%). The 25% decrease in risk is called "relative risk reduction."

◦ Ask your doctor to explain which kind of risk reduction she or he is talking about. Sometimes the numbers can be very misleading.

� What is the potential benefit?

� What is the “cost” to achieve that potential benefit?

AACR Press Release, April 9, 2014: Irregular Menstruation May Predict Increased Risk of Death From Ovarian Cancer

� http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=3325

� Between 1959 and 1967, the Child Health and Development Studies enrolled more than 15,000 pregnant women and followed them for more than 50 years to study factors impacting health during pregnancy. This report is based on 14,403 women who had a single live birth. Cohn and colleagues used medical reports and self-reported data from these women on their menstrual irregularity, including those whose cycles were longer than 35 days, and those who had anovulation. The researchers used this information as a proxy for polycystic ovarian syndrome (PCOS).

� Findings:

◦ Those who had irregular menstrual cycles had a 2.4-fold increased risk of death due to ovarian cancer.

◦ The incidence of late-stage ovarian cancer was twofold higher for women with irregular or infrequent menstrual cycles, and this finding was consistent with their higher risk for death from ovarian cancer.

◦ When the data were analyzed by ovarian cancer type, menstrual irregularities increased risk for serous-type cancers and for endometrioid-type cancers by nearly threefold and fourfold, respectively.

StrengthsStrengths

� MedicalResearch.comhttp://medicalresearch.com/cancer-_-oncology/ovarian-cancer/irregular_menses_linked_to_higher_risk_ovarian_cancer/4856/

� Irregular menses was defined by women’s own report of usual cycle length when women were an average age of 26 years, during an in-person interview.

� The study design was a prospective 50+ year follow-up of 14,403 pregnant women recruited from 1959-1967 to the Child Health and Development Studies (www.chdstudies.org). There were 103 incident cases and 65 ovarian cancer deaths in this study.

� We ruled out the contribution of infertility, the use of fertility drugs, or the use of birth control bills as explanations of study findings. All women in this study had a live birth, and medical records recorded pharmaceuticals prescribed 6 months prior to pregnancy.

� Women with irregular menses constituted 13% of this large pregnancy cohort, and so findings are relevant to many women. Given the lack of information about risk factors, screening or biomarkers for ovarian cancer in young life, our findings offer an opportunity for prevention and for understanding the 90% of ovarian cancer cases that occur in women who do not have rare heritable germlinemutations or family history in a first degree relative.

WeaknessesWeaknesses

� This study does not include infertile women (approx. 10% of all women). The findings are not relevant to risk of ovarian cancer in infertile women.

� There were some tumors with missing data on histology and stage, although there was no evidence that missing data was correlated with irregular menses.

� Other than serous tumors, the sample size for other tumor types was too small for study. However, there was a suggestive finding that risk of death due to endometrioid tumors was also elevated (p=0.14).

� It is estimated that about 80% of women with irregular menses may have polycystic ovarian syndrome (PCOS). However women without significant symptoms (e.g. hirsutism, infertility, obesity) may never be diagnosed with PCOS. Still we cannot determine with certainty whether it is predominantly women with PCOS who were at increased risk of ovarian cancer in this study.

� Unexpected Findings:

◦ Contrary to the existing expectation that PCOS (characterized by less frequent ovulation and irregular/long menstrual cycles) would protect the ovary. But infrequent ovulation is not the only hallmark of PCOS, and there are a number of anatomical, hormonal, and metabolic abnormalities associated with PCOS that might explain the study findings.

What do we do with this information?What do we do with this information?

� Research AdvocateRADAR: Unexpected finding--less frequent ovulation and irregular or long menstrual cycles, expected to protect the ovary. What are anatomical, hormonal, and metabolic abnormalities associated with PCOS that might explain the study findings?

� Research AdvocateRADAR: Is there anything in this study that could yield clues about the etiology of ovarian cancer, and provide opportunities for prevention, early detection for the 90% of ovarian cancers that occur in women without evidence of heritable risk?

� Previvor (or any woman without a cancer diagnosis)ACTION: Record history of menstrual cycle and length (preferably during women’s early reproductive years) and discuss with physician. Even though there are no known effective screening strategies for early detection of ovarian cancer, results of clinical trials in progress, or other advances could provide an opportunity to offer women with irregular cycles screening options in the future.

� Previvor (or any woman without a cancer diagnosis)ACTION: Discuss personal risk and benefits of oral contraceptives with physician. There is evidence that oral contraceptive use correlates with lower risk. Reminder: There is no known effective screening strategy for ovarian cancer at this time.

� Ovarian Cancer SurvivorNOT ACTIONABLE; DISCUSS with family members.

Resources� AACR Webcasts (some are free)

http://webcast.aacr.org/free?link=nav&linkc=my&utm_source=fb&utm_medium=wall&utm_content=free&utm_campaign=2014am

� Walter C. Willett: Diet and cancer: Status report in 2014� http://webcast.aacr.org/console/player/22788?mediaType=podiumVideo&

� Article: http://acsh.org/2014/04/diet-cancer-little-evidence-direct-link/

� 2014 AACR Recaps from Cancer Today magazine http://www.cancertodaymag.org/eventcoverage/Pages/toc.aspx?utm_source=twitter&utm_medium=tweet&utm_content=cancertodaymag&utm_campaign=2014am

� Cancer Today magazinehttp://www.cancertodaymag.org

� AACR Cancer Progress Report 2013 http://cancerprogressreport.org/2013/Documents/2013_AACR_CPR_FINAL.pdf

� ASCO 2014 Ovarian Cancer Abstractshttp://abstracts.asco.org/144/CatAbstView_144_142_AT.html

� Follow ASCO on Twitter: #ASCO14