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OP023/#658 Correlation of hrd status with clinical and survival outcomes in patients with advanced-stage ovarian cancer undergoing frontline and maintenance therapy
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  1. T Sims1,
  2. A Sood2,
  3. S Westin2,
  4. B Fellman3,
  5. J Unke2,
  6. K Rangel2,
  7. T Hilton2 and
  8. N Fleming2
  1. 1The University of Texas MD anderson Cancer Center, Gynecologic Oncology and Reproductive Medicine, Houston, USA
  2. 2The University of Texas MD anderson Cancer Center, Gynecologic Oncology and Reproductive Medicine, Houston, USA
  3. 3The University of Texas MD Anderson Cancer Center, Biostatistics, Houston, USA

Abstract

Objectives We aimed to compare clinical and survival outcomes in high grade ovarian cancer (HGOC) stratified by homologous recombination deficiency (HRD) status undergoing frontline and/or maintenance therapy.

Methods We performed a retrospective analysis of HGOC from April 2013 to June 2019. Clinical outcomes were analyzed by (1) germline BRCA+ (2) germline BRCA - and somatic BRCA/HRD+, or (3) BRCA-/HRD-. Progression free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and modeled via Cox proportional hazards regression.

Results 187 patients met inclusion criteria. 106 patients had germline BRCA mutation, 26 somatic BRCA/HRD+, and 55 BRCA/HRD-. Multivariate analysis for PFS revealed that age (HR 1.02, 95% CI 1.00–1.04), p=0.01), stage (HR 5.7, 95% CI 1.39–23.4, p=0.02), R0 resection at TRS (HR 0.41, 95% CI 0.21–0.83, p=0.01), and BRCA/HRD- status (HR 1.63, 95% CI 1.07–2.48, p=0.02) were significant factors impacting PFS. Multivariate analysis for OS revealed age (HR 1.07, 95% CI 1.03–1.10, p<0.001) and R0 resection at TRS (HR 0.19, 95% CI 0.08–0.44, p<0.001) were significant factors impacting OS. 17 of 187 patients received PARPi maintenance therapy. All harbored a germline or somatic mutation in BRCA1/BRCA2 (14) or had tumors characterized by HRD (3). Multivariate analysis for PFS revealed that PARPi maintenance therapy (HR 0.14 95% CI 0.04–0.57), p=0.006) was a significant factor impacting PFS.

Conclusions Germline BRCA-mutant, somatic BRCA/HRD+ HGOC was associated with improved PFS and OS regardless of primary TRS or NACT. BRCA-/HRD- was a negative prognostic factor for survival in HGOC. PARPi maintenance therapy was associated with improved PFS in Germline BRCA-mutant, somatic BRCA/HRD+ HGOC

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