Case Report: Unexpected Tumour Reduction after PARP Inhibition

After third-line failure, a 61-year-old female patient with metastatic pancreatic ductal adenocarcinoma received off-label monotherapy with olaparib.

Here's what you should take away from this case study

Pancreatic cancer and PARP inhibitors

PARP inhibitors are now established as effective drugs, especially for BRCA-mutated breast and ovarian carcinomas. In addition, in pancreatic ductal adenocarcinoma, the PARP inhibitor Olaparib was recently approved for maintenance therapy in cases of confirmed BRCA germline mutation.

In recent years, PARP inhibitors have become established as effective drugs, particularly for BRCA-mutated breast and ovarian carcinomas. In addition, in pancreatic ductal adenocarcinoma, the PARP inhibitor Olaparib was recently approved for maintenance therapy in cases of confirmed BRCA germline mutation.

However, the approval is made conditional on the affected patients having achieved disease control after receiving platinum-based first-line chemotherapy. This type of PARP-based maintenance therapy has also been shown in trials to have a significant benefit on progression-free survival.

Conversely, there is limited evidence to date for the use of olaparib as monotherapy in BRCA-mutated pancreatic ductal adenocarcinoma after disease progression.

The case: patient with BRCA2 germline mutation

A 61-year-old female patient with a BRCA2 germline mutation underwent treatment for metastatic ductal adenocarcinoma of the pancreas. At the time of admission to the clinic, the woman was already suffering from lung and liver metastases. Before, her case history revealed that she had already survived an advanced breast carcinoma with subsequent local recurrence years before.

With the current pancreatic cancer, she had previously received standard therapies in three lines of treatment. After the third line of treatment had failed, her treating physicians started another line of treatment with an off-label prescription of olaparib.

After only two cycles of the drug, CT scans showed a partial response with complete radiographic regression of the lung metastases. The response and clinical benefit for the patient were maintained after four additional cycles. The radiological and clinical response continued for 6 months.

Olaparib monotherapy in BRCA-positive pancreatic cancer?

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a very poor outlook. The 5-year overall survival (OS) is less than 10%.  What is more, this situation has remained unchanged for more than 50 years.

However, this particular case shows that olaparib in monotherapy could be an option after failure of standard therapy in BRCA-mutated pancreatic cancer. However, caution must be exercised: This is an off-label use of the PARP inhibitor in advanced pancreatic cancer.

Beyond that, this case highlights how important it can be to also consider a therapy with PARP inhibitors once standard therapies have failed. The key factor in deciding on therapy with PARP inhibitors such as olaparib is the outcome of a BRCA test, especially in patients with a possible individual and/or family history of cancer.

Source:
Prete AA et al., Curr Oncol 2022; 29: 544–550.