Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non gBRCAm Ovarian Cancer Patients
Condition: Non-Germline BRCA Mutated Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to assess the efficacy and safety of single-agent olaparib as a
      maintenance treatment in patients with relapsed High Grade Serous Ovarian Cancer (including
      patients with primary peritoneal and/or fallopian tube cancer) or high grade endometrioid
      cancer who do not have known deleterious or suspected deleterious germline BRCA mutations
      (non-gBRCAm) and who had responded following platinum based chemotherapy
    

Detailed description: 
      Maintenance monotherapy with the potent polyadenosine 5'diphosphoribose [Poly (ADP-ribose)]
      polymerisation (PARP) inhibitor (PARPi) olaparib will significantly prolong progression-free
      survival (PFS) in platinum sensitive relapsed non-germline breast cancer susceptibility gene
      (BRCA) mutated ovarian cancer patients who are in complete or partial response following
      platinum based chemotherapy.

      Olaparib is a potent PARPi (PARP-1, -2 and -3) that is being developed as an oral therapy,
      both as a monotherapy (including maintenance) and for combination with chemotherapy and other
      anticancer agents. PARP inhibition is a novel approach to targeting tumours with deficiencies
      in DNA repair mechanisms. PARP enzymes are essential for repairing DNA single strand breaks
      (SSBs). Inhibiting PARP enzymes leads to the persistence of SSBs, which are then converted to
      the more serious DNA double strand breaks (DSBs) during the process of DNA replication.
      During the process of cell division, DSBs can be efficiently repaired in normal cells by
      homologous recombination (HR) repair. Tumours with HR deficiencies (HRDs), such as ovarian
      cancers in patients with BRCA1/2 mutations, cannot accurately repair the DNA damage, which
      may become lethal to cells as it accumulates. In such tumour types, olaparib may offer a
      potentially efficacious and less toxic cancer treatment compared with currently available
      chemotherapy regimens.

      While multiple randomized controlled trials (RCTs) have demonstrated that platinum sensitive
      BRCAm patients have profound response to maintenance treatment with PARP inhibitors, PARP
      inhibitors target cells with homologous recombination deficiency (HRD), of which BRCA
      mutation is only one type. Consistent with the mechanism of action of PARP inhibition,
      response has also been seen in multiple RCTs in patients who are platinum sensitive but whose
      tumours do not harbor BRCA mutations. Presumably these responders have defects in other
      components of HRR pathways, though currently available diagnostic technology is not adequate
      to reliably identify the full spectrum of HRR deficiencies. Instead, these data support the
      hypothesis that platinum sensitivity itself is a clinical selection factor for HRD.
    

Intervention name(s): Olaparib
Intervention type(s): Drug
Intervention description(s): 300 mg twice daily - oral
Other intervention name(s): Lynparza
Intervention MeSH terms: Olaparib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Single arm study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ovarian cancer; non-gBRCA; Platinum; Chemotherapy