An Extraordinary New Treatment Option for Ovarian Cancer: PARP Inhibitors

Ovarian cancers begin in the fallopian tubes and ovaries of women, and some types of ovarian cancer come about through inherited genetic mutations, or mutations passed down from family members. These mutations could determine the therapies you receive during your treatment.

We spoke to Dr. Jose Alejandro Rauh-Hain, gynecologic oncologist from the MD Anderson Cancer Center in Texas, about these hereditary mutations and how they are can be treated by PARP inhibitors, an exciting new treatment in ovarian cancer.

This commonly comes in the form of a BRCA mutation, the same genetic mutation that is a risk factor for breast cancer. If an ovarian cancer is caused by a BRCA mutation, then a PARP inhibitor, a treatment that targets cancer cells, could be an effective treatment.

BRCA Mutations and PARP Inhibitors

Tumor cells with BRCA mutations have problems repairing DNA already, and the PARP inhibitors make that worse, causing cancer cells to die. “What we have seen,” says Dr. Rauh-Hain, “is that if patients have those kind of mutations … if they receive those medications the chances of the cancer coming back are much lower,  and the patients that have received those medications actually live longer.”

The PARP inhibitor Lynparza (olaparib) is approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.

When Are PARP Inhibitors Used?

Until recently, PARP inhibitors had been used for women who have undergone surgery and 4-6 rounds of previous chemotherapy. Emerging data from clinical trials, however, now supports the use of these inhibitors upfront, as part of the initial course of treatment.

While PARP inhibitors are now available to almost all women, women with BRCA gene mutations or who are HRD proficient may benefit the most from these drugs. The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer irrespective of whether the tumor is HRD or the patient has the BRCA gene.

The American Society of Clinical Oncology (ASCO) guidelines recommend PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.

Due to limited benefit in progression free survival seen in the absence of HRD, gynecologic oncologists differ on whether PARP inhibitors should be universally recommended in the “upfront maintenance setting.” Each patient should be made aware of risks and benefits to PARP inhibitor maintenance and decide with their oncologist what is the best treatment plan for them.

The PARP inhibitor Lynparza (olaparib) is approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.

Lynparza is also approved in combination with Avastin (bevacizumab) for women with HRD. Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.

PARP Inhibitors for Recurrent Cancer

Unfortunately, too often, ovarian cancer comes back.

For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Lynparza, Zejula and another PARP inhibitor called Rubraca (rucaparib) are FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.

For some women who have had prior chemotherapy treatments, Rubraca, Zejula or Lynparza may also be options. These uses are based on factors such as number of prior therapies and BRCA mutation or HRD.

Learn more about the side effects of PARP inhibitors here.