Rucaparib May Have Potential Clinical Benefit for Advanced Pancreatic Cancer

Rucaparib, an (ADP-ribose) polymerase (PARP) inhibitor approved for the treatment of ovarian cancer, may have potential clinical benefit for patients with advanced pancreatic cancer and a BRCA1/2 mutation, according to study findings.

With a poor prognosis and limited treatment options, pancreatic cancer is projected to become the second leading cause of cancer death by 2020. Approximately 9% of pancreatic cancers have a BRCA1 or BRCA2 mutation. As studies of BRCA1/2 mutations in breast and ovarian cancer have shown clinical benefit with PARP inhibitors, researchers sought to determine the clinical benefit in patients with pancreatic cancer.

The global, phase 2 study enrolled 19 patients aged 18 and older with locally advanced or metastatic pancreatic cancer with a known BRCA1/2 mutation between April 2014 and April 2016. Patients could have received up to 2 prior lines of chemotherapy but could not have received prior therapy with a PARP inhibitor.

Patients received 600 mg tablets of rucaparib twice daily until disease progression or other reasons for discontinuation. The patients ranged from age 41 to age 75. Of the 19 patients, 16 had germline mutations, and 3 had somatic mutations.

The confirmed overall response rate was 15.8% (95% CI, 3.4%-39.6%), and 4 patients achieved a response. Two patients had confirmed partial responses, and 1 patient had a complete response. A fourth patient had an unconfirmed complete response.

The disease control rate—complete response, partial response, or stable disease for 12 or more weeks—was 31.6% (6 of 19) in all patients and 44.4% (4 of 9) in those who received 1 prior chemotherapy regimen.

As prespecified in the protocol, trial enrollment was stopped because of an insufficient response rate in the first 15 patients. However, the responses seen in BRCA-mutant patients were durable and clinically significant, according to the authors of the study. They wrote: “Our findings suggest that there may be a role for PARP inhibition in patients with a BRCA1/2 mutation, particularly in those whose disease has not progressed while taking prior platinum chemotherapy.”

The authors underscored the importance of looking outside chemotherapy options for patients with pancreatic cancer, particularly for those with potentially targetable mutations. They also highlighted the importance of these results for opening the door for targeting BRCA mutations in other cancers.

“These results not only point us in a new treatment direction to further investigate for patients with pancreatic cancers, but it also reinforces the clinical significance of the BRCA genes beyond ovarian and breast cancer and the utility of PARP inhibitors in other cancers,” said Susan M. Domcheck, MD, executive director, Basser Center for BRCA at the Abramson Cancer Center, University of Pennsylvania, in a statement.

They concluded by recommending that future studies focus on better understanding the sequencing of PARP inhibitor treatment and potential maintenance therapy, as well as potential predictors of resistance to therapy.

Reference:

Shroff R, Hendifar A, McWilliams R, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precision Oncology. doi: 10.1200/PO.17.00316.