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The increasing importance of pathology in modern clinical trial conduct: OlympiA as a case in point

  • Lauren Kalinowski
    Affiliations
    The University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Qld, Australia

    Department of Histopathology, Sullivan Nicolaides Pathology, Bowen Hills, Brisbane, Qld, Australia
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  • Giuseppe Viale
    Affiliations
    European Institute of Oncology IRCCS, University of Milan, Milan, Italy
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  • Susan Domchek
    Affiliations
    Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
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  • Andrew Tutt
    Affiliations
    Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK

    Breast Cancer Now Unit, The School of Cancer Studies and Pharmaceutical Science, King's College London, London, UK
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  • Peter C. Lucas
    Affiliations
    University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center, Pittsburgh, PA, USA
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  • Sunil R. Lakhani
    Correspondence
    Address for correspondence: Prof Sunil Lakhani, The University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Qld 4029, Australia.
    Affiliations
    The University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Qld, Australia

    Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane, Qld, Australia
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      Recently published results from the randomised phase III adjuvant therapy OlympiA trial are a significant development for patients with hereditary breast cancer in the era of precision medicine. OlympiA has shown adjuvant treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor significantly improves outcomes in patients with germline BRCA-mutated early breast cancer.
      • Tutt A.N.J.
      • Garber J.E.
      • Kaufman B.
      • et al.
      Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer.
      ,
      • Tutt A.N.J.
      • Garber J.
      • Gelber R.D.
      • et al.
      Pre-specified event driven analysis of overall survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. ESMO virtual plenary sessions.
      PARP inhibitors are already approved for use in Australia in patients with germline BRCA1/2 mutations that have either high stage, high grade ovarian carcinomas or metastatic HER2-negative breast cancer. The American Society of Clinical Onocology (ASCO), National Cancer Comprehensive Network (NCCN) and St Gallen Early Breast Cancer Consensus updated guidelines now also include treatment with olaparib to improve outcomes for patients with an inherited mutation in BRCA1 or BRCA2 with early stage, HER2-negative breast cancer who have a high recurrence risk based on the results of OlympiA.
      • Tutt A.N.J.
      • Garber J.E.
      • Kaufman B.
      • et al.
      Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer.
      ,
      • Tung N.M.
      • Zakalik D.
      • Somerfield M.R.
      Hereditary breast cancer guideline expert panel. Adjuvant PARP inhibitors in patients with high-risk early-stage HER2-negative breast cancer and germline BRCA mutations: ASCO hereditary breast cancer guideline rapid recommendation update.

      National Comprehensive Cancer Network. Breast cancer. Cited 11 Feb 2022. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

      • Burstein H.J.
      • Curigliano G.
      • Thurlimann B.
      • et al.
      Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.
      The United States Food and Drug Administration (FDA) approved the PARP inhibitor olaparib in high recurrence risk early breast cancer patients with germline BRCA1/2 mutations in March 2022.

      US Food and Drug Administration. FDA approves olaparib for adjuvant treatment of high-risk early breast cancer. Updated 11 Mar 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-adjuvant-treatment-high-risk-early-breast-cancer.

      A large number of ongoing clinical trials are examining olaparib and other PARP inhibitors in early breast cancer. These recent advances are bringing PARP inhibitors into the clinic for early breast cancer patients. As more targeted therapies become available and new prognostic and predictive biomarkers emerge, the role that pathologists play in clinical trials and in changing clinical practice is becoming increasingly important.
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