PARP inhibitors can shrink tumors in pancreatic cancer patients with specific mutations

April 02, 2019

ATLANTA - Switching pancreatic cancer patients to the PARP inhibitor rucaparib as maintenance therapy instead of continuing intensive chemotherapy either shrunk tumors or stopped them from growing in 17 of 19 patients in an interim analysis from a trial at the Abramson Cancer Center at the University of Pennsylvania. The results are from a study evaluating this therapy in patients with BRCA1, BRCA2, or PALB2 mutations and provides encouraging early evidence that this approach might control cancer growth in patients who carry these genetic mutations. Kim Reiss Binder, MD, an assistant professor of Hematology-Oncology in Penn's Perelman School of Medicine and the study's lead author, will present the findings in a news conference today at the 2019 American Association for Cancer Research Annual Meeting in Atlanta (Abstract #7643).

Pancreatic cancer is responsible for more cancer deaths in the United States each year than any cancer type other than lung and colorectal, despite the fact that it only accounts for about three percent of annual new cancer cases. Just 8.5 percent of patients survive five years with the disease. Between six and eight percent of pancreatic cancer patients have a BCRA or PALB2 mutation, and this subgroup usually responds well to platinum-based chemotherapy.

"Patients with BRCA or PALB2 mutations do exceptionally well with platinum chemotherapy, however the cumulative side effects of chemotherapy can make the treatment intolerable over time," Reiss Binder said. "Using a PARP inhibitor as maintenance therapy could provide a less toxic option for patients, so we wanted to test this strategy."

Rucaparib is currently approved by the U.S. Food and Drug Administration as a maintenance therapy for patients with ovarian and fallopian tube cancer whose disease has recurred but is responding to platinum-based chemotherapy. For this study, Reiss Binder and the Penn team used it in the same way for pancreatic cancer patients with BRCA or PALB2 mutations. The study is still ongoing, but so far the early results are promising. Of the 19 patients evaluated at the last data cutoff, one had a complete response and six more had a partial response. The disease control rate - which is defined as the total number of patients experiencing a complete response, partial response, or stable disease - was 90 percent for at least eight weeks. The median progression-free survival was 9.1 months.

"The data is extremely preliminary, but the fact that we're seeing complete and partial responses for some of these patients is very exciting, as this is a population that doesn't have many options to treat one of the deadliest forms of cancer," Reiss Binder said, noting that patients with advanced pancreatic cancer often only have chemotherapy as an option. "To be able to offer a targeted therapy with much less toxicity, even if only for a subset of our patients, would be a wonderful thing," she said.

Overall, rucaparib was well tolerated. Eight patients in this study have remained on rucaparib for at least six months, and two patients have remained on it for more than a year. The most common side effects were nausea, a change in taste, and fatigue, but none were serious enough to require any of the patients to stop treatment.

"These promising results highlight just how crucial it is for cancer patients to undergo genetic testing, as specific mutations can help guide doctors to targeted therapies and treatment strategies," said the study's senior author Susan Domchek, MD, executive director of the Basser Center for BRCA at Penn.

Researchers note this is an interim analysis of an ongoing trial, so further study and validation is still needed on this approach.

The press briefing for this study will begin at 8:30 a.m. in Room B309. In addition, Reiss Binder will present these results as a clinical trials mini-symposium at 3:00 p.m. in Marcus Auditorium, Building A-GWCC.
This study was supported by Clovis Oncology, which manufactures rucaparib.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided more than $500 million to benefit our community.

University of Pennsylvania School of Medicine

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