PARP INHIBITORS FOR PANCREATIC CANCER

Patients with advanced pancreatic cancer harboring BRCA or PALB2 mutations and who respond to chemotherapy may be candidates for maintenance therapy with the poly ADP-ribose polymerase (PARP) inhibitor rucaparib (Rubraca, Clovis Oncology), according to results reported today at the American Association for Cancer Research (AACR) 2019 annual meeting.

In an interim analysis of an ongoing phase 2 study, objective response rate was 36.8% and median progression-free survival was 9.1 months.

"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," Kim Reiss Binder, MD, assistant professor of medicine in the Division of Hematology Oncology at the University of Pennsylvania in Philadelphia, said in an AACR press release.

"This is a preliminary and early signal, which indicates that we can potentially do better than chemotherapy for a small group of patients [with BRCA and PALB2mutations]," Reiss Binder told Medscape Medical News.

In Pancreatic Cancer, No Chemotherapy Forever

Reiss Binder noted that between 6% and 8% of patients with pancreatic cancer harbor pathogenic BRCA or PALB2 mutations. These mutations readily respond to platinum-based chemotherapies, but the quality of life with persistent chemotherapy is significantly compromised for patients with pancreatic cancer due to cumulative toxicities, she pointed out.

"This approach often becomes unsustainable," she said. "In these patients we can move toward a model of induction chemotherapy followed by maintenance therapy with rucaparib," she added. Reiss Binder explained that this kind of study opens the door for expanding maintenance therapy to other patients, perhaps with targeted agents or biologic therapies.

"Effective maintenance therapy in this setting means no chemotherapy forever," she said.

Reached for comment, Efrat Dotan, MD, medical oncologist at Fox Chase Cancer Center in Philadelphia, agreed.

In the last few years, new data have emerged to identify a subgroup of patients with pancreatic cancer who harbor mutations in DNA repair mechanism genes (such as BRCA) and have significant response to platinum-based chemotherapy, she explained. Recent data from the Pancreatic Cancer Action Network's Know Your Tumor program found these mutations in about 17% of patients with pancreatic cancer, and demonstrated their improved survival with the use of platinum-based therapy, she noted.

"This maintenance treatment approach [with rucaparib] is highly valuable in providing these patients with a treatment that will keep the disease at check without the toxicities associated with platinum-based chemotherapy," she said.

"Despite the small number of patients, the results are encouraging and warrant further evaluation in a larger clinical trial," she added.