PARP Inhibitor Shows Promise in Patients With BRCA-Mutated Pancreatic Cancer

Key Points

  • Of the 19 patients treated, 4 had responses and 2 additional patients had stable disease.
  • The objective confirmed response rate, the primary endpoint for the study, was 16% (3/19).
  • About 9% of patients have BRCA1/2 mutation–associated pancreatic cancer.

A targeted therapy that has been effective in fighting ovarian cancer in women, including those with BRCA1 and BRCA2 mutations, may also help patients with aggressive pancreatic cancer who harbor these mutations and have few or no other treatment options. An international team of researchers was led by the Perelman School of Medicine and the Basser Center for BRCA at the University of Pennsylvania. Shroff et al reported their findings in JCO Precision Oncology.

The poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib (Rubraca), which was approved by the U.S. Food and Drug Administration (FDA) in April 2018 for the treatment of women with ovarian cancer who have recurrent disease or received prior therapies, showed its clinical benefit in previously treated pancreatic patients with BRCA mutations in a phase II clinical trial. Of the 19 patients treated, 4 had responses and 2 additional patients had stable disease.

About 9% of patients have BRCA1/2 mutation–associated pancreatic cancer.

“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. Domchek, MD, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania.

PARP is an enzyme used by healthy cells to repair themselves. However, cancer cells also use PARP to repair DNA damage, thus extending their growth and possible lethality. Preliminary results from the study, which included patients from seven centers around the world, were presented at the 2016 ASCO Annual Meeting (Abstract 4110). These latest findings represent the full study.

More on the Recent Findings

The trial included 11 men and 8 women, with a median age of 57. Twenty-one percent of the patients had BRCA1 mutation–associated pancreatic cancer, while 79% were associated with BRCA2 mutations.

Importantly, Dr. Domchek said, none of the patients who benefited from rucaparib had tumors that had progressed on a prior platinum-based chemotherapy, suggesting a potential role for rucaparib as an earlier treatment for patients whose tumors are not resistant to such treatments.

Overall, a clinical benefit was observed in 32% of patients (6/19) treated with rucaparib, and 45% in patients (4/9) who had received only one prior chemotherapy for locally advanced or metastatic disease. Nine patients had progressive disease, and 3 were not evaluable for response. The objective confirmed response rate, the primary endpoint for the study, was 16% (3/19).

“Consideration should be given to use of this therapy for treatment of patients whose tumors have not progressed on prior platinum therapy,” the authors wrote. “Future studies should focus on better understand the sequencing of PARP inhibitor treatment and potential maintenance therapy, as well as potential predictors of resistance to therapy.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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