Clinical case of therapy for BRCA1-associated metastatic pancreatic cancer

The article presents a clinical case of a patient with BRCA1-associated metastatic pancreatic cancer (mPC) who received first-line chemotherapy with mFOLFIRINOX followed by a transition to maintenance therapy with olaparib (300 mg 2 times a day). During the treatment, significant regression of the tumor and liver metastases, normalization of the CA-19-9 level (from 952 to 7 U/ml) were achieved. The patient underwent conditional radical surgery to remove the primary tumor, and olaparib therapy was continued. The clinical case illustrates the effectiveness of targeted therapy with PARP inhibitors in patients with BRCA1/2 mutations and emphasizes the importance of genetic testing in PCa and gives reason to think about the place of PARP inhibitors in adjuvant therapy. Nowadays olaparib is the standard of care for patients with gBRCA-mutated (including BRCA1) mPCa who have achieved disease control on first-line platinum-based chemotherapy. Long-term results are encouraging, demonstrating the potential for long-term disease control in a significant proportion of patients. Data on response to therapy and survival indicate a significant discrepancy in the effectiveness of treatment for patients with or without mutations. Thus, the median overall survival (OS) in BRCA-positive mPC without therapy is 8–12 months (which is comparable to sporadic mPC), and with chemotherapy (FOLFIRINOX/gemcitabine + cisplatin) it reaches 18–22 months. Maintenance therapy with olaparib after treatment with platinum drugs increases progression-free survival (PFS): 7.4 months versus 3.8 months without therapy. This indicates the high significance of BRCA1/2 testing in PC. The issue of surgical treatment of patients with mPCa who have responded positively to therapy remains highly controversial and requires further study. There is insufficient data on the adjuvant (after radical surgery) therapy regimen, but studies are underway (APOLLO, NCT04858334).

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