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PARP Inhibitors Now Used for First- and Second-Line Maintenance of Ovarian Cancer

 

For many years, the standard of care for newly diagnosed advanced ovarian cancer (including fallopian tube and primary peritoneal cancer) has been surgery and paclitaxel plus platinum-based chemotherapy. However, this regimen has not provided favorable outcomes for many patients.

“Standard of care provides relief from the disease, but the number of patients experiencing relapse is close to 80 percent,” said Angela Jain, MD, a Fox Chase medical oncologist specializing in the treatment of gynecologic cancer. “Although most patients with recurrent ovarian cancer receive multiple lines of therapy, this cancer is generally considered incurable.”

Recently, the use of PARP inhibitors has changed the way ovarian cancer is treated and has improved outcomes.

In 2014, the PARP inhibitor olaparib was FDA approved as maintenance therapy for women with recurrent BRCA-mutated ovarian cancer following three lines of therapy. Two years later, rucaparib was approved for use after two lines of therapy, and studies also hinted at its effectiveness in women with homologous recombination deficiency (HRD) mutations.  

“The game changer came with the approval of niraparib in 2017 for post-platinum maintenance of all ovarian cancers—this eliminated specific mutation restrictions,” said Jain. “It gave all platinum sensitive ovarian cancer patients the option to be treated with a PARP inhibitor for maintenance treatment.”

Newly published data on first-line maintenance with niraparib showed significantly longer progression-free (PFS) survival with niraparib (13.8 months) vs. placebo (8.2 months). Also, since its original approval in 2014, olaparib has been approved as first-line maintenance for patients with BRCA mutations and complete or partial response to platinum-based chemotherapy.

Due to the success of these and other currently approved PARP inhibitors, research on other PARP inhibitors is also underway. PARP inhibitors are also being studied in combination with other drugs to improve their effectiveness for all ovarian cancer patients.

According to Jain, PARP inhibitors are appealing to both oncologists and patients for a variety of reasons, and the latest findings are enabling oncologists to explore these medications as a treatment option for many patients.

“Patients are looking for better options to prevent or delay recurrence, and PARP inhibitors are attractive to them because they are taken orally. This means that patients spend less time in infusion centers,” said Jain. “The new data give us something to discuss with our patients. Some individuals may want to benefit from prolonged progression-free survival, while others may not be ready for maintenance therapy with PARP inhibitors, as they can be associated with adverse effects like neuropathy, fatigue, and indigestion. Regardless, the point is that physicians and patients now have more options for fighting ovarian cancer.”

Things to Know About PARP Inhibitors and Ovarian Cancer

  • The age of carboplatin and paclitaxel being the only frontline treatment option for certain patients with advanced ovarian, fallopian, and primary peritoneal cancer is over.

  • Newly published data on first-line maintenance with niraparib showed significantly longer progression-free (PFS) survival with niraparib (13.8 months) vs. placebo (8.2 months). Also, since its original approval in 2014, olaparib has been approved as first-line maintenance for patients with BRCA mutations and complete or partial response to platinum-based chemotherapy.