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330 Complete surgical cytoreduction remains pivotal in achieving better survival outcomes in patients with advanced ovarian cancer with a BRCA1/2 germline mutation in the pre-parp inhibitor ERA
  1. Mohamed Otify,
  2. Alexandros Laios,
  3. Hannah Elkadi,
  4. Angelika Kaufmann,
  5. Sarika Munot,
  6. George Theophilou,
  7. Amudha Thangavelu,
  8. David Nugent,
  9. Tim Broadhead,
  10. Richard Hutson and
  11. Diderick De Jong
  1. St James’s University Hospital; Leeds Teaching Hospitals; Gynaecologic Oncology


Introduction/Background Ovarian malignancies arising in patients with germline BRCA1/2 mutations are characterised by increased platinum sensitivity. It is not known if this feature should be considered when choosing between primary surgical and neoadjuvant therapy at the time of diagnosis. We hypothesised that patients with BRCA 1/2 germline mutations have a better response to neoadjuvant chemotherapy, and their surgery may be less extended to achieve a complete surgical cytoreduction. We aimed to compare pre-operative, intra-operative, and survival parameters between patients with and without a BRCA 1/2 germline mutation.

Methodology A total of 168 prospectively registered BRCA 1/2 typed women with a diagnosis of advanced ovarian cancer (AOC) at St James’s Institute of Oncology, Leeds, who underwent cytoreductive surgery following neoadjuvant chemotherapy between October 2013 and October 2018 were identified. Primary outcomes included progression-free survival (PFS) and overall survival (OS). Secondary outcomes included chemotherapy response score (CRS), performance status (PS) and residual disease (RD). Differences between BRCA-positive and BRCA-negative groups were analysed using Stata 13®. P < 0.05 was considered as statistically significant.

Results Patients with a complete surgical cytoreduction had longer OS compared to those with an optimal or sub-optimal cytoreduction (48 vs 31 months, p=0.0001). PS and CRS were independent predictors for PFS, irrespective of BRCA status (p=0.00001 and 0.00006). There was no significant difference between BRCA mutation carriers and non-carriers for mean PFS and OS (19 vs 18 months, and 50 vs 42 months, p=0.69 and 0.39, respectively). BRCA mutation carriers had no better chemo response or less extended surgery to achieve a complete surgical cytoreduction following neoadjuvant chemotherapy compared to non-carriers (p=0.67 and 0.5, respectively). In the subgroups of patients with a PS of 2 and those receiving single-agent chemotherapy, BRCA mutation carriers had shorter OS than non-carriers (RR 0.4 and 0.31, 95% CI 0.17–0.91 and 0.1–0.93, p=0.029 and 0.037, respectively). In the subgroup of patients with a CRS of 3, BRCA mutation carriers had longer PFS and OS than non-carriers (RR 12.5 and 20.8, 95% CI 3.32–47.6 and 4.8–88.8, p=0.00 and 0.00, respectively).

Conclusion Complete surgical cytoreduction remains pivotal in achieving better survival outcomes in AOC women, irrespective of BRCA status. A survival benefit is unlikely for patients with poor PS, and those receiving single-agent chemotherapy. A favourable response to neoadjuvant chemotherapy or less extended surgery to achieve a complete surgical cytoreduction in patients with a BRCA 1/2 germline mutation could not be confirmed.

Disclosures No Conflict of interest or any disclosure to make.

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