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Data + Perspectives: Biologic Basis and Available Clinical Research Underlying the Protocol and Nonresearch Use of PARP Inhibition in Patients with Ovarian and Breast Cancer
Released June 2018

Proceedings from a CME symposium held at the 2018 AACR Annual Meeting. Featuring perspectives from Drs Ursula A Matulonis, Kathleen Moore, Mark Robson and Andrew Tutt. (Video Program)

CE Information and Faculty Disclosures

  • TARGET AUDIENCE
    This activity is intended for medical oncologists, hematologists, surgeons, radiation oncologists, oncology nurses and other healthcare professionals involved in basic, translational and clinical cancer research or treatment.

    OVERVIEW OF ACTIVITY
    Over the past 2 decades, the oncology community has witnessed a significant transformation in the way clinicians think about the diagnosis and treatment of cancer. During this time, a shift has occurred from a “one-size-fits-all” approach to one in which therapeutic decision-making is routinely informed by the presence of molecular alterations and/or relevant biomarkers. Given that one tumor type may share a number of biologic similarities with another, it is not surprising that researchers have attempted to apply knowledge and therapeutic understanding across multiple diseases, yielding a growing body of evidence illustrating that a single therapy can provide benefit for patients with the same genetic abnormality but an entirely different disease. Although it has long been established that women with a BRCA1/2 mutation are at higher risk of developing breast and ovarian cancer, it was not until recently that the therapeutic significance of these abnormalities was documented. Specifically, it has now been established that patients with these diseases and a BRCA1/2 mutation are sensitive to treatment with a PARP inhibitor. In addition, the efficacy of these agents may not be restricted to this population, and a number of strategies have been explored to select patients without these mutations who may still benefit. This new understanding has created an array of clinical, translational and practical questions across the oncology research and care continuum.

    These video proceedings from a CME symposium held during the 2018 AACR Annual Meeting feature discussions with leading ovarian and breast cancer researchers regarding actual patient cases and related clinical research findings. By providing information on important developments, this activity will assist medical oncologists and other healthcare professionals to address existing management uncertainties and determine the current and future roles of PARP inhibition in these diseases.

    LEARNING OBJECTIVES

    • Appraise available guideline recommendations and consensus statements regarding the indications and evidence-based modalities for genetic testing in ovarian and breast cancer, and use the results of these assessments to guide long-term treatment planning, including clinical trial recruitment.
    • Understand the biologic rationale for the investigation of PARP inhibition for ovarian and breast cancer, and use this insight to inform protocol and nonresearch therapy and future clinical trial design.
    • Appreciate available clinical trial data with FDA-approved PARP inhibitors for ovarian cancer to safely integrate these agents into routine clinical care.
    • Appreciate the recent FDA approval of olaparib for patients with HER2-negative metastatic breast cancer harboring a germline BRCA mutation, and discern how this agent can be appropriately and safely integrated into routine clinical practice.
    • Recognize the toxicities associated with PARP inhibitors commonly used in the treatment of breast and ovarian cancer, and offer supportive management strategies to minimize and/or ameliorate these side effects.
    • Describe mechanisms of acquired tumor resistance to PARP inhibitors, and identify investigational therapeutic opportunities to circumvent this process.
    • Develop an understanding of the mechanisms of action, available data and potential clinical roles of other investigational PARP inhibitors in preparation for their possible availability.

    ACCREDITATION STATEMENT
    Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

    CREDIT DESIGNATION STATEMENT
    CME credit is no longer available for this issue

    AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
    CME credit is no longer available for this issue

    HOW TO USE THIS CME ACTIVITY
    This CME activity consists of a video component.
    CME credit is no longer available for this issue

    CONTENT VALIDATION AND DISCLOSURES
    Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education. We assess conflicts of interest with faculty, planners and managers of CME activities. Conflicts of interest are identified and resolved through a conflict of interest resolution process. In addition, all activity content is reviewed by both a member of the RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

    FACULTY — The following faculty (and their spouses/partners) reported relevant conflicts of interest, which have been resolved through a conflict of interest resolution process:

    Ursula A Matulonis, MD
    Medical Director and Program Leader
    Gynecologic Oncology Program
    Professor of Medicine
    Harvard Medical School
    Dana-Farber Cancer Institute
    Boston, Massachusetts

    Advisory Committee: 2X Oncology, FUJIFILM Pharmaceuticals USA Inc, GeneDx, ImmunoGen Inc, Myriad Genetic Laboratories Inc; Consulting Agreements: 2X Oncology, FUJIFILM Pharmaceuticals USA Inc, GeneDx, ImmunoGen Inc, Merck, Myriad Genetic Laboratories Inc.

    Kathleen Moore, MD
    Jim and Christy Everest Endowed Chair in Cancer Research
    Director, Oklahoma TSET Phase I Program
    Stephenson Cancer Center
    Associate Professor, Section of Gynecologic Oncology
    Director, Gynecologic Oncology Fellowship
    Department of Obstetrics and Gynecology
    University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma

    Advisory Committee: AstraZeneca Pharmaceuticals LP, Genentech BioOncology, Janssen Biotech Inc; Consulting Agreements: Abbott Laboratories, Astellas Pharma Global Development Inc, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb Company, Exelixis Inc, Genentech BioOncology, GlaxoSmithKline, Incyte Corporation, Janssen Biotech Inc, Lilly, Merck, Novartis, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Roche Laboratories Inc, Sanofi Genzyme, Takeda Oncology.

    Mark Robson, MD
    Clinic Director, Clinical Genetics Service
    Associate Attending Physician, Clinical Genetics and Breast Cancer Medicine
    Associate Member
    Memorial Sloan Kettering Cancer Center
    Associate Professor of Medicine
    Weill Medical College of Cornell University
    New York, New York

    Advisory Committee, Consulting Agreement and Contracted Research: AstraZeneca Pharmaceuticals LP.

    Andrew Tutt, MB ChB, PhD
    Consultant Oncologist/Director
    Breakthrough Breast Cancer Research Unit
    King’s Health Partners Academic Health Science Centre
    London, United Kingdom

    Advisory Committee: AstraZeneca Pharmaceuticals LP, EMD Serono Inc.

    EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following commercial interests: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Adaptive Biotechnologies, Agendia Inc, Agios Pharmaceuticals Inc, Amgen Inc, Ariad Pharmaceuticals Inc, Array BioPharma Inc, Astellas Pharma Global Development Inc, AstraZeneca Pharmaceuticals LP, Baxalta Inc, Bayer HealthCare Pharmaceuticals, Biodesix Inc, bioTheranostics Inc, Boehringer Ingelheim Pharmaceuticals Inc, Boston Biomedical Pharma Inc, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, CTI BioPharma Corp, Dendreon Pharmaceuticals Inc, Eisai Inc, Exelixis Inc, Foundation Medicine, Genentech BioOncology, Genomic Health Inc, Gilead Sciences Inc, Halozyme Inc, ImmunoGen Inc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Kite Pharma Inc, Lexicon Pharmaceuticals Inc, Lilly, Medivation Inc, a Pfizer Company, Merck, Merrimack Pharmaceuticals Inc, Myriad Genetic Laboratories Inc, NanoString Technologies, Natera Inc, Novartis, Novocure, Onyx Pharmaceuticals, an Amgen subsidiary, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Prometheus Laboratories Inc, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, Seattle Genetics, Sigma-Tau Pharmaceuticals Inc, Sirtex Medical Ltd, Spectrum Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro Inc, Teva Oncology and Tokai Pharmaceuticals Inc.

    RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

    This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantor.

    This activity is supported by an educational grant from AstraZeneca Pharmaceuticals LP.

    Hardware/Software Requirements:
    A high-speed Internet connection
    A monitor set to 1280 x 1024 pixels or more
    Internet Explorer 11 or later, Firefox 56 or later, Chrome 61 or later, Safari 11 or later, Opera 48 or later
    Adobe Flash Player 27 plug-in or later
    Adobe Acrobat Reader
    (Optional) Sound card and speakers for audio

    Last review date: June 2018
    Expiration date: June 2019

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