Long-Term Survival With Olaparib Maintenance Therapy in Metastatic Pancreatic Carcinoma of a Patient Harboring Germline BRIP1 and ATM Mutations.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the United States, causing approximately 50,000 deaths annually. Among PDAC patients, those with germline BRCA1/2 mutations show a more favorable response to platinum-based chemotherapy and PARP inhibitors like olaparib. The 2019 randomized placebo-controlled double-blind Phase 3 POLO trial demonstrated olaparib's efficacy as a first-line maintenance therapy in patients with BRCA-mutated metastatic PDAC following platinum-based chemotherapy. Olaparib was subsequently approved by the FDA, EMA, and PMDA. However, this treatment approach has not been extended to other homologous recombination deficiency (HRD)-related mutations. This case report details a 72-year-old white, female patient with cogermline mutations in the ATM and BRIP1 genes, both of which are involved in DNA repair pathways, resulting in HRD. Following a diagnosis of metastatic PDAC, the patient achieved complete remission after retreatment with FOLFIRINOX and has maintained remission for over 40 months on olaparib maintenance therapy. Her ongoing remission, coupled with undetectable levels of circulating tumor DNA, supports olaparib's potential effectiveness in HRD-positive PDAC beyond BRCA mutations. This case highlights the need for expanded HRD testing and consideration of PARP inhibitor maintenance therapy for PDAC patients with HRD pathway deficiencies. Our findings advocate for further clinical studies to assess the broader applicability of PARP inhibitors in PDAC patients with HRD mutations, including ATM and BRIP1, which could enhance survival outcomes in this high-risk population. Expanding the standard of care to include PARP inhibitors for HRD-positive PDAC could address a critical gap in treatment and improve patient prognosis.