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Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)

Author

Listed:
  • Elizabeth M. Swisher

    (University of Washington)

  • Tanya T. Kwan

    (Clovis Oncology, Inc.)

  • Amit M. Oza

    (University Health Network)

  • Anna V. Tinker

    (BC Cancer—Vancouver)

  • Isabelle Ray-Coquard

    (GINECO, Centre Léon Bérard and University Claude Bernard)

  • Ana Oaknin

    (Vall d’Hebron Institute of Oncology (VHIO))

  • Robert L. Coleman

    (MD Anderson Cancer Center)

  • Carol Aghajanian

    (Memorial Sloan Kettering Cancer Center)

  • Gottfried E. Konecny

    (University of California Los Angeles)

  • David M. O’Malley

    (James Cancer Center)

  • Alexandra Leary

    (Gustave Roussy Cancer Center and INSERM U981)

  • Diane Provencher

    (l’Université de Montréal (CHUM))

  • Stephen Welch

    (Lawson Health Research Institute)

  • Lee-may Chen

    (University of California San Francisco Helen Diller Family Comprehensive Cancer Center)

  • Andrea E. Wahner Hendrickson

    (Mayo Clinic)

  • Ling Ma

    (Rocky Mountain Cancer Centers)

  • Prafull Ghatage

    (Tom Baker Cancer Center)

  • Rebecca S. Kristeleit

    (Guy’s and St. Thomas NHS Foundation Trust)

  • Oliver Dorigo

    (Stanford University Cancer Center and Stanford Cancer Institute)

  • Ashan Musafer

    (Austin Hospital)

  • Scott H. Kaufmann

    (Mayo Clinic)

  • Julia A. Elvin

    (Foundation Medicine, Inc.)

  • Douglas I. Lin

    (Foundation Medicine, Inc.)

  • Setsuko K. Chambers

    (University of Arizona Cancer Center)

  • Erin Dominy

    (Clovis Oncology, Inc.)

  • Lan-Thanh Vo

    (Clovis Oncology, Inc.)

  • Sandra Goble

    (Clovis Oncology, Inc.)

  • Lara Maloney

    (Clovis Oncology, Inc.)

  • Heidi Giordano

    (Clovis Oncology, Inc.)

  • Thomas Harding

    (Clovis Oncology, Inc.)

  • Alexander Dobrovic

    (Austin Hospital)

  • Clare L. Scott

    (Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research)

  • Kevin K. Lin

    (Clovis Oncology, Inc.)

  • Iain A. McNeish

    (Imperial College London)

Abstract

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity.

Suggested Citation

  • Elizabeth M. Swisher & Tanya T. Kwan & Amit M. Oza & Anna V. Tinker & Isabelle Ray-Coquard & Ana Oaknin & Robert L. Coleman & Carol Aghajanian & Gottfried E. Konecny & David M. O’Malley & Alexandra Le, 2021. "Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22582-6
    DOI: 10.1038/s41467-021-22582-6
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