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PARP inhibitor rucaparib helps shrink pancreatic tumors with mutations

Journal of Clinical Oncology
Reuters Health - 11/05/2021 - Most patients with pancreatic cancer and BRCA1/2 or PALB2 mutations had tumor shrinkage or no tumor growth after switching from chemotherapy to the oral PARP inhibitor rucaparib as maintenance therapy in a phase-2 study.

"This is another step forward for PARP inhibitors and for the treatment of tough-to-treat pancreas tumors," lead researcher Dr. Kim Reiss of the University of Pennsylvania Perelman School of Medicine, in Philadelphia, said in a news release.

"It's a safe option that not only has the potential to maintain responses, but also shrink pancreatic tumors and, in some cases, achieve complete responses for those carrying these mutations," said Dr. Reiss.

Rucaparib is currently approved in the United States as a maintenance therapy for certain patients with prostate cancer or recurrent ovarian, fallopian tube or primary peritoneal cancer, but not pancreatic cancer.

The investigator-initiated, single-arm study enrolled 46 patients with advanced pancreatic cancer with germline (g) or somatic (s) pathogenic variants (PVs) in BRCA1, BRCA2, or PALB2 who had received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was stopped and patients received oral rucaparib (600 mg twice daily) until cancer progression.

Among 42 evaluable patients, 27 had gBRCA2, seven gBRCA1, six gPALB2, and two sBRCA2.

With a progression-free survival (PFS) rate at six months of 59.5%, "the study met its primary objective," Dr. Reiss and her colleagues report in the Journal of Clinical Oncology. The PFS rate at 12 months was 54.8%.

"We observed striking activity of maintenance rucaparib," they add, with a median PFS of 13.1 months and median overall survival of 23.5 months.

The objective response rate was 41.7% and included three complete responses and 12 partial responses. The disease-control rate (complete or partial response or stable disease) was 66.7% for a median time of 17.3 months.

"Importantly, we observed activity in patients with gPALB2 PVs and sBRCA2 PVs and in a patient with squamous cell carcinoma, suggesting that the role of poly (ADP-ribose) polymerase inhibitors might be expanded in clinical practice," the authors say.

According to a university news release, "At the cutoff date of the study, eight patients remained alive and in active follow-up more than two years after starting rucaparib, of which four are progression-free. Of the three patients with complete responses, two remain ongoing today after more than a year."

No new safety signals were noted.

In email to Reuters Health, Dr. Reiss said, "This was a single institution, single arm study, and the results should therefore be interpreted with some caution. But based on our results, I do think that rucaparib is a safe and effective treatment for platinum-sensitive, advanced pancreatic cancer with pathogenic germline or somatic BRCA1, BRCA2 or PALB2 variants."

These results demonstrate that rucaparib is "another effective and less toxic maintenance therapy option for pancreatic cancer patients and underscore the importance of genetic counseling and testing, which can potentially steer the treatment course in a better direction," senior author Dr. Susan Domcek, executive director of the Basser Center for BRCA at Penn, said added in the news release.

The study was supported by Clovis Oncology, the Basser Center Young Leadership Council, The Konner Fund, The Pearl and Philip Basser Innovation Research Award and an Anonymous Foundation.

SOURCE: https://bit.ly/3o6OYda Journal of Clinical Oncology, online May 10, 2021.

By Megan Brooks

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