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Treatment patterns after poly-ADP ribose polymerase (PARP) inhibitors in epithelial ovarian cancer patients
  1. Tharani Sivakumaran1,
  2. Michael Krasovitsky2,3,
  3. Alison Freimund1,
  4. Yeh Chen Lee2,3,
  5. Kate Webber4,5,
  6. Jane So4,
  7. Christie Norris2,
  8. Michael Friedlander2,3,
  9. Linda Mileshkin1,6 and
  10. George Au-Yeung1,7
  1. 1Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
  2. 2Department of Medical Oncology, Prince of Wales Hospital and Royal Hospital for Women, Randwick, New South Wales, Australia
  3. 3University of New South Wales Prince of Wales Clinical School, Randwick, New South Wales, Australia
  4. 4Department of Medical Oncology, Monash Health, Clayton, Victoria, Australia
  5. 5School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
  6. 6Department of Gynaecological Oncology, Mercy Hospital for Women, Heidelberg, Victoria, Australia
  7. 7Oncology and Dysplasia, The Royal Women's Hospital, Parkville, Victoria, Australia
  1. Correspondence to Dr George Au-Yeung, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; George.Au-Yeung{at}petermac.org

Abstract

Objectives The primary objective of this study was to describe treatment patterns after poly-ADP ribose polymerase (PARP) inhibitor in patients with epithelial ovarian cancer. Secondary objectives were to evaluate duration of response, time to first subsequent therapy, progression-free survival and overall survival.

Methods This was a retrospective analysis of patients with epithelial ovarian cancer treated with PARP inhibitor therapy at six Australian gynecological oncology centers. Eligible patients were identified via clinics, trial databases and pharmacy dispensing logs between January 2005 and September 2019. Information regarding clinico-pathological characteristics and treatment outcomes were collated from medical records.

Results A total of 85 patients with epithelial ovarian cancer were identified. Of these, 61% had germline BRCA1/2 mutations, 9% had somatic BRCA1/2 mutations, 5% had confirmed homologous recombination deficiency and 25% were BRCA1/2 wildtype mutations. A total of seventy-seven (91%) patients received chemotherapy after PARP inhibitor, with fifty-six (72.7%) of these patients receiving platinum-based chemotherapy. Four patients (5%) had a complete response, 15 (20%) a partial response, 15 (20%) stable disease and 41 (55%) progressive disease. Median duration of response to chemotherapy was 7.0 months (range 0.2–20.4). Median time to first subsequent therapy was 17.6 and 15.1 months in patients who received a PARP inhibitor as maintenance therapy and treatment, respectively. Median progression-free survival of first line treatment after PARP inhibitor was 9.6, 3.5 and 4.6 months for platinum doublet, single agent platinum and non-platinum chemotherapy, respectively. Adjusting for age and FIGO (Federation of Gynecological Oncologists classification) stage progression-free survival did not differ between treatment groups (p=0.14). Median overall survival for the cohort was 69 months, and patients with platinum sensitive ovarian cancer had improved survival compared with those with platinum refractory or resistant disease.

Conclusion Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds.

  • Ovarian Cancer
  • BRCA1 Protein
  • BRCA2 Protein
  • Medical Oncology

Data availability statement

Data may be obtained from a third party and are not publicly available.

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Data availability statement

Data may be obtained from a third party and are not publicly available.

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Footnotes

  • Twitter @Dr_TSivakumaran

  • Contributors TS: conceptualization, data curation, formal analysis and original draft, review and editing the manuscript, revision of manuscript and guarantor. MK: conceptualization, data curation, formal analysis and original draft, review and editing the manuscript, revision of manuscript. AF: review and editing of manuscript, revision of manuscript. YCL: conceptualization, supervision and review and editing of manuscript, revision of manuscript. KW: review and editing of manuscript, revision of manuscript. JS: data collection. CN: identification of eligible patients. MF: review and editing of manuscript, revision of manuscript. LM: supervision and review and editing of manuscript, revision of manuscript. GA-Y: conceptualization, supervision and review and editing of manuscript, revision of manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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