Olaparib Maintenance Therapy in Ovarian Cancer with BRIP1 Mutation

Introduction to BRIP1 and HRD

BRIP1 is a gene associated with homologous recombination deficiency (HRD), similar to BRCA1/2, suggesting potential sensitivity to PARP inhibitors 1
Tumors with HRD show greater benefit with PARP inhibitors according to NCCN 1

The American Society of Clinical Oncology (ASCO) 2020 guidelines recommend olaparib maintenance (300 mg orally every 12 hours for 2 years) for women with newly diagnosed stage III-IV ovarian cancer with germline or somatic BRCA1/2 mutations who are in complete or partial response after platinum-based chemotherapy 2, 3
This recommendation is based on high-quality evidence and has a strong strength of evidence, based on the SOLO1 study 2, 3
The National Comprehensive Cancer Network (NCCN) 2019 classifies olaparib as a category 1 recommendation for germline BRCA1/2 mutations and a category 2A recommendation for somatic BRCA1/2 mutations 4, 5

Niraparib is approved for all women with advanced ovarian cancer in response to first-line chemotherapy, regardless of BRCA status, based on the PRIMA study 2, 3
The benefit of niraparib was significant in patients without BRCA1/2 mutations but with HRD positive status (HR 0.71) 6
The combination of olaparib + bevacizumab may be offered to patients with genomic instability determined by Myriad myChoice CDx, even without BRCA1/2 mutation 2, 7

In the PAOLA-1 study, patients without BRCA1/2 mutations but with HRD positive status (defined by GIS ≥42 in MyChoice CDx) showed significant benefit of PFS with olaparib + bevacizumab versus bevacizumab alone 6
NCCN indicates that in the absence of BRCA1/2 mutation, HRD status can provide information about the magnitude of benefit of PARP inhibitor therapy (category 2B) 6
Patients with HRD negative status did not show significant benefit (HR 1.00; 95% CI 0.75-1.35) 7

For platinum-sensitive recurrent ovarian cancer, PARP inhibitors are strongly recommended as maintenance therapy, regardless of BRCA mutation status 1
Patients with HRD positive status, including those with BRIP1, may benefit from PARP inhibitors, although the evidence is not specific to BRIP1 1

For first-line therapy, confirm HRD status using a validated test (MyChoice CDx or other FDA/CLIA-approved test) 5, 8
If HRD positive and complete/partial response to platinum-based chemotherapy, consider niraparib (category 2A) as first option, or olaparib + bevacizumab if bevacizumab was received in first-line therapy (category 2B for HRD without BRCA) 6, 9
For recurrent disease sensitive to platinum, offer PARP inhibitor maintenance therapy (olaparib 300 mg every 12 hours, rucaparib 600 mg every 12 hours, or niraparib 200-300 mg/day) 1

There is no FDA approval for olaparib in patients with isolated BRIP1 mutation without BRCA1/2 mutation 5, 9
The evidence for BRIP1 is extrapolated from HRD studies, not from specific studies for this gene 1
Patients with HRD negative status should not receive olaparib as monotherapy maintenance 7, 6