Duration of PARP Inhibitor Maintenance Therapy in Patients With Ovarian Cancer With Germline or Somatic BRCA Mutations.

BACKGROUND: Defects in BRCA1/2, which are tumor suppressor genes involved in the process of homologous recombination repair, can result in ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors target these defects by further preventing DNA repair. Molecular analysis demonstrates a high rate of loss of heterozygosity (LOH) in patients with germline BRCA1/2 mutations and/or those with BRCA-associated cancers. Conversely, LOH is rare in patients with somatic BRCA1/2 mutations, prompting hypotheses that tumors with somatic BRCA mutations have a distinct phenotype compared with tumors with germline BRCA mutations. Treatment guidelines recommend using PARP inhibitors in patients with germline or somatic BRCA mutations for ovarian cancer maintenance therapy. However, the duration of maintenance therapy with PARP inhibitors based on germline versus somatic mutation status has not been directly compared, and many prospective trials included a small number of patients with somatic BRCA mutation tumors. OBJECTIVE: To compare the duration of maintenance therapy with PARP inhibitors in patients with ovarian cancer with germline BRCA mutations versus somatic BRCA mutations. METHODS: This single-center, retrospective, observational analysis included adults with ovarian cancer who were receiving maintenance therapy with PARP inhibitors at UNC Medical Center between December 2018 and April 2021. The primary outcome was the duration of maintenance therapy with PARP inhibitors. The secondary outcomes included the rate of dose interruptions, reductions, and discontinuation resulting from adverse events and the rate of LOH testing. RESULTS: A total of 21 patients met the study's eligibility criteria, of which 14 (67%) patients had a BRCA1 mutation (11 germline BRCA mutations and 3 somatic BRCA mutations). The remaining 7 (33%) patients had a BRCA2 mutation (6 germline BRCA mutations and 1 somatic BRCA mutation). The median duration of PARP inhibitor therapy was 18.5 months for patients with a germline BRCA mutation and 20.1 months for those with a somatic BRCA mutation (P=.46). Most of the study patients had dose interruptions (60% each in the germline BRCA and somatic BRCA mutation groups) and/or reductions (60% with germline BRCA mutation vs 80% with somatic BRCA mutation) as a result of adverse events during the study period. The discontinuation of treatment with PARP inhibitors as a result of adverse events was 30% in the germline BRCA mutation group versus 20% in the patients with a somatic BRCA mutation. None of the 21 patients in the study had LOH testing. CONCLUSION: Among the patients with ovarian cancer who received maintenance therapy with PARP inhibitors, there was no significant difference in the duration of the therapy with PARP inhibitors between the patients with germline BRCA mutation and those with somatic BRCA mutation. Larger patient populations and more data regarding the correlation of LOH to the response rate are needed to determine the best biomarker to predict a benefit from maintenance therapy with PARP inhibitors. [ABSTRACT FROM AUTHOR]