More than two-thirds of pancreatic cancer patients with genetic mutations have had their tumors stop growing or shrink considerably after switching from intensive chemotherapy to the PARP inhibitor rucaparib as a maintenance treatment, researchers from Abramson Cancer Center (ACC) of the University of Pennsylvania reported online today in the Journal of Clinical Oncology. CCA Phase II Trial Results Support Use of Rucaparib in Pancreatic Cancer Patients BRCA1, BRCA2, and PALB2 variants to help control tumor growth without the harsh side effects of chemotherapy.
Rucaparib – a targeted therapy in pill form – is currently approved by the United States Food and Drug Administration as a maintenance treatment for patients with recurrent ovarian and fallopian tube cancer. and prostate cancer, but not pancreatic cancer.
“This is another step forward for PARP inhibitors and for the treatment of difficult-to-treat pancreatic tumors,” said Kim Reiss, MD, assistant professor of hematology-oncology at Penn’s Perelman School of Medicine and author principal of the study. “It is a safe option that has the potential not only to maintain responses, but also to shrink pancreatic tumors and, in some cases, to obtain complete responses for those who carry these mutations.”
Arnold Simon, 71, who was first diagnosed in 2016 with metastatic pancreatic cancer and later found out he had the BRCA2 mutation, is one such patient. One of the first participants in the trial, Simon has been on rucaparib for over three years. Since then, each of his last 16 CT scans has been clear with no signs of active cancer.
“The biggest advantage of being on the PARP inhibitor is that it is just pills, and the side effects have been minimal,” Simon said. “I don’t have to sit down and run off chemotherapy for six hours. As far as I’m concerned, for me, there’s nothing better than what I am now.”
Rucaparib is the second PARP inhibitor to show benefit in patients with pancreatic cancer and BRCA germline mutations, and the first to show efficacy in those with PALB2 germline mutations and somatic mutations in BRCA. Lydia Henson, a 56-year-old patient who was diagnosed with metastatic pancreatic cancer in 2014, was treated with chemotherapy for years before finding out she had the PALB2 mutation, which led to her being tested ACC. She has been taking the PARP inhibitor for 18 months with no signs of active cancer.
Of the 42 patients with advanced pancreatic cancer evaluated in the study, 12 had a partial response and three a complete response.
The disease control rate – which is defined as the total number of patients with complete response, partial response, or stable disease – was 66.7% for a median of 17.3 months. The median progression-free survival was 13.1 months and the overall survival 23.5 months.
At the study cut-off date, eight patients remained alive and in active follow-up for more than two years after starting treatment with rucaparib, four of whom are progression-free. Of the three patients with complete responses, two remain ongoing today after more than a year, including Henson.
Rucaparib has also shown benefit in patients with acinar squamous cell carcinoma of the pancreas, further expanding the population for which these drugs could be used.
Pancreatic cancer is responsible for more cancer deaths in the United States each year than any other type of cancer other than lung and colorectal, despite only accounting for about 3% of new cancer cases. annual. Only 10 percent of patients survive five years with the disease. Between six and eight percent of pancreatic cancer patients have a BRCA or PALB2 mutation.
The study follows preliminary data from an interim analysis of the trial presented in 2019 at the annual meeting of the American Association for Cancer Research.
“These latest results show us another effective and less toxic maintenance treatment option for patients with pancreatic cancer,” said lead study author Susan Domchek, MD, executive director of the Basser Center for BRCA to Penn, “and stress the importance of genetic counseling and testing, which can potentially point treatment in a better direction.”
Penn co-authors include Rosemarie Mick, Mark H. O’Hara, Ursina Teitelbaum, Thomas Karasic, Charles Schneider, Stacy Cowden, Traci Southwell, Janae Romeo, Natallia Izgur, Zain M. Hannan, Rashmi Tondon, Katharine Nathanson, Robert H. Vonderheide, Max M. Wattenberg and Gregory Beatty.