Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers

Gynecol Oncol. 2019 Nov;155(2):262-269. doi: 10.1016/j.ygyno.2019.09.008. Epub 2019 Oct 8.

Abstract

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice.

Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy.

Results: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125.

Conclusions: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.

Keywords: BRCA mutation; Maintenance; Olaparib; Ovarian cancer; PARP inhibitor; Prognostic; Survival.

Publication types

  • Multicenter Study

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • CA-125 Antigen / metabolism
  • Disease-Free Survival
  • Female
  • Genes, BRCA1 / physiology
  • Genes, BRCA2 / physiology
  • Germ-Line Mutation / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Phthalazines / therapeutic use*
  • Piperazines / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CA-125 Antigen
  • Phthalazines
  • Piperazines
  • olaparib