2016 AACI Parker 8/2/2018 Precision Medicine National Institute of - PDF document

2016 AACI Parker 8/2/2018 Precision Medicine • National Institute of Health Precision Medicine Initiative 2015: “Prevention and treatment strategies that take individual patients into account”… • Individualizing care based upon genes, Precision Medicine Approaches for Treatment environment, and prognosis and Early Detection of Breast Cancer • Targeting therapies to specific patients, tumors, and pathways Barbara Parker, MD Professor of Medicine • Targeting screening strategies to patients at Division of Hematology/Oncology highest risk Senior Deputy Director of Cancer Medicine UC San Diego Moores Cancer Center June 26 2018 Disclosure Information Change in Cancer Treatment Past Decade Prior Standard of Care I have the following financial relationships to disclose: Patient’s Chemotherapy, tissue sample Hormone therapy pathology • Grant/research support recipient grade, size, IHC Precision Medicine – GlaxoSmithKline -> Novartis – Genentech/Roche Targeted therapy PP PPP P P Patient’s Molecular P P and/or P tissue sample diagnostics • Stock Shareholder P Immunotherapy P P P P P P – Merck Which pathways are active? • Consultant fees Examples: Her2 amplification, BRAF, KRAS, ALK, EGFR – Bioalta mutations, Microsatellite status Modified courtesy of Emile Voest, MD 5 Outline Breast Cancer Risk Factors Age, Gender, and Race • • Breast Cancer and Precision Medicine Benign Breast Disease • • Breast Cancer Incidence and Death rates Personal history of breast cancer • • Treatment Advances Lifestyle and diet – migration studies • – Metastatic breast cancer – Obesity, poor exercise, alcohol – Early Stage - High Risk cancers Reproductive and hormonal factors • – Early Stage - Low Risk cancers – Early periods, late menopause, late births Athena Breast Health Network • – Menopause hormonal therapy – University of California - 5 cancer centers collaboration using precision medicine to advance Family history and genetic factors • screening and treatment Ionizing radiation (Hodgkin’s survivors) • 1

2016 AACI Parker 8/2/2018 Diverging Needs Several Subtypes of Breast Cancer To Shift High Risk to Low Risk Cancers Higher Risk Cancers Lower risk cancers • • Subtype ER+ Her2 – Triple Neg Her2 + Innovation Challenge Incidence 65% 15% 20% Management challenge Innovation in tumor and patient Careful selection of therapy • • Mammo detected Yes Yes Yes selection to guide therapy Minimize side effects • Interval cancer No Yes Yes Public health initiatives to shift Address subsets of patients • Study use of less toxic therapy • higher risk to lower risk: Therapeutic innovation to Peak recurrence > 5 years < 5 years < 5 years • Improve health care systems • reduce recurrence risk and screening, genetics, prevention, Early stage Standardization • improve survival lifestyle risk reduction, Chemo response Poor Good Good Access • education, and models of care Disparities • Brain metastases Uncommon Common Common Survivorship • Course of Slow: years Fast: months to Slow in 80% Quality metrics • years Fast in 20% metastases Integration of multi-disciplinary care • Burstein H, SABCS 2014 Burstein H, SABCS 2014 Metastatic Breast CA Breast Cancer Recurrence According to Subtype and Time of Diagnosis Advances in Treatment ER+ Her2 - • Patients doing much better due to – New CDK4/6 inhibitors very effective • Enhanced screening – MTOR inhibitors effective • High quality multi-disciplinary care – Certain mutations (ESR1) predict endocrine resistance • Widespread use of endocrine, chemotherapy Triple negative • and biologic therapy – Olaparib, a PARP inhibitor, FDA approved for BRCA1/2 carriers – Androgen Receptor subset targeting promising Stage I-III breast cancers from British Columbia Cancer Agency – Immunotherapy alone or in combination promising 1986-1992 2004-2008 – Other novel agents promising (e.g. sacituzumab) Her2 + • – First line Chemo + two Her2 targeting antibodies – Second line: Kadcyla – a drug-antibody conjugate – Her2 mutation – targeted therapy under study (neratinib) – Lapatinib + Herceptin (non chemo) effective Rachel J.D. Cossetti et al. JCO 2015;33:65-73 Metastatic Breast Cancer Diverging Needs Patient Flow Lower risk cancers • Higher Risk Cancers • Biopsy of metastatic site Management challenge Innovation Challenge ER/PR/Her2 – send for Careful selection of therapy • Innovation in tumor and patient • Molecular Profiling Tumor and Blood Minimize side effects • selection to guide therapy Study use of less toxic therapy • Address subsets of patients • Improve health care systems • Therapeutic innovation to • First Line Rx Profiling tumor reduce recurrence risk and Standardization • improve survival Clinical Trial or and blood Access • Disparities • standard chemo Survivorship • Quality metrics • Second Line Rx Integration of multi-disciplinary care • Olaparib pills if Clinical Trial or BRCA1/2 standard chemo Burstein H, SABCS 2014 2

2016 AACI Parker 8/2/2018 I-SPY 2 TRIAL TAILORx Take Home Points High Risk Early Stage For patients over the age of 50 with scores less 26 • Stage II-III Surgery to Serial there is NO benefit to adjuvant chemotherapy Chemo +/- Breast determine if Breast MRIs Novel Agent cancer and biopsy cancer is – 75% of patients enrolled in the trial High Risk at 3 weeks gone For patients < age 50 (especially with scores of 21-15) • there may be a small benefit to chemotherapy – Unclear if benefit from induction of menopause • Goal to identify drugs that have promise – Requires careful discussion with patient • Multiple arms match therapies to breast cancer subtypes Results have changed the standard of care • Trial design minimizes patients needed (typically < 100) • • New agents “graduate” if they reach a certain benefit Accrual >2300 pts in 20 sites (Laura Esserman MD, Study PI) >300 pts at UCSD (Anne Wallace MD and team) Immunotherapy Results Exciting SUMMARY High Risk Early Stage - ISPY2 Advances in Breast Cancer Treatment Subtype determines treatment Percent of patients with disappearance of cancer Metastatic breast cancer • 70 – New drugs and novel combinations effective 60 50 – Patients living longer with ”chronic disease” 40 Early Stage – High Risk Stage II and Stage III • 30 – Novel drugs + chemo prior to surgery very promising 20 and may accelerate FDA approval (e.g. ISPY2) 10 Early Stage – Lower Risk Stage I and Stage II • 0 – Molecular profiling determines the majority of ER+ Her2 - Triple Neg All patients Standard Pembrolizumab patients who can avoid chemotherapy Nanda R ASCO 2017 TAILORX Clinical Trial Low Risk Early Stage Athena Breast Health Network • Purpose is rapid integration of research into clinical care • Established network • 5 University of California cancer centers • 13 Midwest hospitals (Sanford Health) • 100+ providers and researchers in multidisciplinary fields • Clinical Care and Research Teams • 125,000+ women enrolled to date PI: Laura Esserman MD • Largest initiative is the Wisdom Study SSparano J et al NEJM June 2018 3

2016 AACI Parker 8/2/2018 Athena Accomplishments • 125,000 women completed standardized mammo form – >75% agree to have data used for research – >60% agree to be contacted for future research – About 10% at elevated risk • Breast oncology standards shared by UCSF and UCSD – Automate services and referrals • Pathology harmonization – Score the Core (Hum Pathol 2015) • Radiology harmonization – Inter-reader variability (Acad Radiol 2017) • Radiation Oncology practice patterns – (Clin Breast Cancer 2015) Athena Strategic Initiatives • Personalized risk assessment as part of screening Prevention • Prevention counseling for high risk women • Risk based screening and prevention • Tailored frequency Screening and Diagnosis • Fewer false positives • Who is at risk for what type of cancer Treatment • Tailored interventions based on molecular profiling Survivorship • Better models of care 4