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PARP inhibitors for maintenance therapy of pancreatic cancer

April 3, 2019 13:21

According to results presented at the annual meeting of the American Association for Cancer Research, for patients with advanced cancer of the pancreas with BRCA mutations or PALB2 and those who respond to chemotherapy can be useful rukaparibom supportive therapy, an inhibitor of poly-ADP-ribose polymerase.

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The interim analysis of the Phase 2 study of response to treatment was 36.8% and the average progression-free survival - 9.1 months.

"Some of the patients showed a complete or partial response to treatment rukaparibom This suggests that therapy can not only maintain the treatment, but in some cases, to reduce the tumor,." - says Kim Binder Reiss, MD, assistant professor of medicine at the University of Pennsylvania. She noted that 6-8% of patients with pancreatic cancer or BRCA observed PALB2 mutation. These mutations are easily respond to chemotherapy based on platinum, but the quality of life a constant chemotherapy significantly reduced because of toxicity.

"Now we can go to the induction chemotherapy model c rukaparibom supportive therapy - she adds -. The effective maintenance therapy in these conditions means that chemotherapy is not eternal."

In the past few years, new data for identification of the subgroup of patients with pancreatic cancer who have mutations in the DNA repair mechanism genes that demonstrate a response to chemotherapy based on platinum. In 17% of patients with pancreatic cancer were observed improvement in survival rates.

"This approach to maintenance treatment using rukapariba very important for treatment of these patients, which will control the disease without the toxicity associated with chemotherapy based on platinum - explains Binder -. Despite the small number of patients, the results are encouraging and require further evaluation in a larger clinical trial. "

Thierry Conroy, MD, also pointed out that the use of olapariba was also positive for the same group of patients in maintenance treatment of advanced pancreatic cancer. Olaparib is the first inhibitor of PARP, which is likely to be approved for the maintenance treatment of pancreatic cancer.

Based on this model - induction therapy followed by maintenance therapy target - studies were designed progressive pancreatic cancer for assessing maintenance therapy with a combination of PARP inhibitor and immunotherapeutic agents such as ipilimumab or nivolumab.

Rukaparib supports approved as a drug for patients with recurrent ovarian cancer and uterine tubes, which respond to chemotherapy based on platinum. "We wanted to determine whether you can use this therapeutic strategy in patients with pancreatic cancer with tumors sensitive to platinum" - says Reiss Binder.

The average age of patients was 61 years, 16 of them women, and 4 patients were less than 16 weeks of induction chemotherapy. Side effects included nausea (43.4%), dysgeusia (34.8%) and fatigue (26.1%).

With a median follow 257 days, the average progression-free survival was 278 days (9.1 months). Because 36.8% of the total response indicator 1 patient showed a complete response, 6 patients showed a partial response. Eight patients were on maintenance treatment rukaparibom for more than 6 months and two patients continued treatment for more than 1 year. Of the 7 patients who respond to supportive therapy, and 4 had mutations in BRCA2 germline, 2 had mutations in PALB2, and 1 was a somatic mutation in BRCA2.

Source: https://www.medscape.com/viewarticle/911215#vp_1

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