ASCO 2016: Rucaparib Shows Clinical Benefit in BRCA-Mutated Pancreatic Cancer


Key Points

  • In this phase II study of patients with pancreatic cancer who had received prior chemotherapy in the locally advanced or metastatic setting, treatment with the PARP inhibitor rucaparib resulted in an objective response rate of 16%.
  • The disease control rate for all patients was 32% and for those who received one prior line of chemotherapy was 50%.
  • Rucaparib had previously shown benefit in patients with BRCA-mutated ovarian cancer. About 9% of patients with pancreatic cancer harbor BRCA1/BRCA2 mutations.

The targeted PARP inhibitor rucaparib, which has demonstrated robust clinical activity in patients with ovarian cancer who have a BRCA mutation, also showed promise in previously treated patients with pancreatic cancer who have the mutation, according to results from a phase II clinical study presented by Domchek et al at the 2016 ASCO Annual Meeting (Abstract 4110).

Overall, a clinical benefit was observed in 32% of patients (6 of 19) treated with rucaparib. Of the 19 patients with pancreatic cancer, 1 had a complete response and 2 had partial responses, whereas 4 patients had stable disease. The objective response rate, the primary endpoint for the study, was 16% (3 of 19).

"These results are encouraging and further demonstrate the clinical significance of the BRCA cancer genes outside of breast and ovarian, and not just in women," said Susan M. Domchek, MD, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania. "It points us to a potential new treatment avenue for pancreatic cancer, an aggressive disease that's often caught in the later stages. Though smaller in number, some patients with advanced disease and carrying a BRCA mutation may benefit from the same targeted therapy being used today in the clinic to successfully treat some ovarian cancer patients."

About Rucaparib

Recent studies have shown that rucaparib effectively treats patients with platinum-sensitive, relapsed, high-grade ovarian cancer harboring a BRCA mutation. In a study presented at ASCO in 2015, researchers showed that treatment resulted in a 69% RECIST (Response Evaluation Criteria in Solid Tumors) response rate in these patients. In April 2015, it received a U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation. 

The success in ovarian patients prompted a clinical study in pancreatic patients with the same mutation; about 9% of pancreatic patients are BRCA1/BRCA2 positive.

Study Details

The team enrolled participants with measurable, relapsed disease who received one to three prior rounds of chemotherapy for locally advanced or metastatic cancer. The trial included 11 male and 8 female patients, with a median age of 57 years. Twenty-one percent of the patients tested positive for the BRCA1 mutation, and 79% tested positive for the BRCA2 mutation.

The disease control rate (defined as partial response or stable disease for more than 12 weeks) for all patients was 32% (6 of 19) and 50% (3 of 6) in patients who received one prior line of chemotherapy. Four patients had stable disease, nine patients had progressive disease, and three were not evaluable for response. One patient was on the drug for 72 weeks and is continuing to receive the drug.

Rucaparib had an acceptable safety profile. Common treatment-emergent side effects included nausea (63%) and anemia (47%).

All patients who responded received only one prior line of chemotherapy therapy, suggesting that the drug may be an option earlier in the treatment course.

The study was sponsored by Clovis Oncology.

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®.