#9 PARP Inhibitors for Maintenance Therapy in Ovarian Cancer

Overview

No cancer diagnosis is easy news, but for some types, the news hits harder. Depending on its stage, a diagnosis of ovarian cancer could be the worst news a woman may ever hear. With its non-specific symptoms and lack of early detection tests, around 20 percent of cases are found early – leaving an overwhelming 80% of diagnoses with less than favorable chances of survival. In women ages 35-74, ovarian cancer is the fifth leading cause of cancer-related deaths, and with a stat like one in 78 women developing ovarian cancer in her lifetime, innovation for improved outcomes is long overdue.

Maintenance therapy is a therapy designed to help a primary treatment succeed. The best example of maintenance therapy is in cancer – through which chemotherapy, hormonal therapy, or targeted therapy are used to prevent or delay the cancer’s return after an individual has achieved remission. In some types of cancer, maintenance therapy is well explored. But in other cancers, like ovarian cancer, maintenance therapy is less established.

The treatment landscape for ovarian cancer has seen great change in the past few years. Patients newly diagnosed with the condition are typically treated with surgery and 6 to 8 cycles of chemotherapy over 4-6 months. While most patients respond, many eventually become resistant, giving the condition its characteristic of relapse. Around 2011, PARP inhibitors made their way into the space, showing benefits in patients with recurrent cancer. In the past few years, however, PARP inhibitors have piqued the interest of oncologists for even broader use – such as an agent for maintenance therapy.

PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase, better known as PARP. They function by disenabling repairs to single strand breaks in the DNA of tumors. After DNA replication with single strand breaks present, double strand breaks will form. In tumors with BRCA1, BRCA2 and PALB2 mutations, these double strand breaks cannot be efficiently repaired, ultimately leading to cell death. Healthy, non-tumor cells still have homologous DNA repair operating and are therefore able to survive the inhibition of PARP.

2018 marked the first PARP inhibitor to receive FDA approval as a maintenance therapy after first line  chemotherapy in women with ovarian cancer and a BRCA1 or BRCA2 mutation. Results from a phase III study released earlier this year, served as the basis for this approval with the PARP inhibitor showing 70% reduction in the risk of recurrence at three years.

There are several late-stage trials currently exploring the use of PARP inhibitors in ovarian cancer with at least two other agents currently pursuing, or having received, approval for the maintenance therapy indication. In addition to demonstrating improved progression free survival, researchers hope that PARP inhibitor use will show improved long term outcomes. Others hope this targeted therapy could even become a first line therapy. But today, to maintain outcomes, PARP inhibitors are equipping women for the lengthy fight and helping to better digest the unnerving diagnosis of ovarian cancer.
 

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