Maintenance treatment with the PARP inhibitor rucaparib (Rubraca) was well tolerated and provided clinical responses among patients with advanced BRCA- or PALB2- mutated pancreatic cancer sensitive to platinum-based chemotherapy, according to results from an interim analysis of an ongoing phase II clinical trial presented at the AACR Annual Meeting 2019.
Rubraca is sponsored by Clovis Oncology.
“In this interim analysis, we are finding that patients with platinum-sensitive pancreatic cancer appear to benefit from treatment with single agent rucaparib,” Kim Reiss Binder, assistant professor of medicine in the Division of Hematology Oncology at The Hospital of The University of Pennsylvania, said in a statement.
“Several patients had complete or partial responses with rucaparib treatment, suggesting that this therapy has the potential not only to maintain the disease, but also to shrink the tumors in some instances,” Reiss Binder said.
Approximately 6 to 8% of patients with pancreatic cancer harbor pathogenic mutations in the genes BRCA or PALB2, Reiss Binder said. Mutations in these genes often coincide with susceptibility to platinum-based chemotherapies, she said.
“While this subgroup of pancreatic cancer patients respond well to platinum-based chemotherapy, prolonged treatment leads to cumulative toxicity, so this approach often becomes unsustainable,” said Reiss Binder. “We wanted to investigate more tolerable maintenance options, as there are no approved treatments in this setting.”
Rucaparib was approved as a maintenance treatment for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who respond to platinum-based chemotherapy.
This single-arm, phase II clinical trial is actively enrolling patients with advanced BRCA- or PALB2-mutated pancreatic cancer who have not progressed on prior platinum-based chemotherapy. The patients in the interim analysis had received a median of four months of prior platinum chemotherapy. More than 80% of patients were female.
Patients are treated with 300mg of rucaparib twice daily until disease progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival. Overall response rate is also being evaluated.
Nineteen of the 24 enrolled patients were evaluable for analysis as of Dec. 31, 2018.
The median PFS at time of analysis was 9.1 months following initiation of rucaparib treatment. The ORR was 37%, which included one complete response and six partial responses. The disease control rate (defined as the sum of PR, CR, and stable disease) was 90% for at least eight weeks. Eight patients remained on rucaparib therapy for at least six months, and two patients have remained on rucaparib therapy for more than one year.
“Although this is very preliminary data, the fact that we’re seeing sustained clinical responses in some of these patients is very exciting,” said Reiss Binder. “Other than the recent tissue- agnostic approval of pembrolizumab for patients with microsatellite instability-high tumors, there really is no other targeted therapy that has shown promise for patients with pancreatic cancer.
“Our results highlight the importance of germline and somatic testing in pancreatic cancer patients,” said Reiss Binder. “The presence of certain mutations can guide treatment strategies, and patients should know to ask their oncologist about getting tested.”
As this was an unplanned interim analysis of an ongoing, small, single-arm study, the results require substantial further validation.
This study is sponsored by the Abramson Cancer Center and is funded by Clovis Oncology. Reiss Binder receives research funding from Clovis Oncology, Tesaro, Bristol-Myers Squibb, and Lilly Oncology.
