Who Can Have PARP Inhibitors?

There is an encouraging new wave of treatments for women with ovarian cancer called PARP inhibitors. PARP inhibitors keep cancers from growing by blocking their ability to repair DNA, ultimately killing off cancer cells. These drugs originally were only used in patients with BRCA mutations who had a cancer recurrence after 2 or more rounds of chemotherapy.  But there is new data that supports expanded use for women with or without a BRCA mutation as maintenance therapy after platinum-based chemotherapy. We spoke to some of the top gynecologic oncologists in the world about who is eligible for PARP inhibitors.

Here’s the quick checklist of who may be eligible for PARP inhibitors, according to the experts:

1. Women who could use them as maintenance therapy, which occurs after initial surgery and multiple rounds of chemotherapy (i.e. in women with advanced/recurrent ovarian cancer) for patients with a BRCA mutation.
2. Women who could use them as maintenance therapy after platinum-based chemotherapy for recurrent ovarian cancer in women with or without a BRCA mutation.
3. Women who could use them as initial therapy if the women have a BRCA mutation after initial surgery and chemotherapy to prevent first recurrence for advanced ovarian cancer.
4. Women with BRCA mutations who have had a least 2 prior chemotherapy regimens and whose cancer still comes back.
5. A clinical trial is exploring whether PARP inhibitors can be used by women as initial therapy following initial surgery and chemotherapy in women with or without a BRCA mutation.

Note: There are three types of PARP inhibitors–Olaparib, Rucaparib, and Niraparib

If you’re interested, here are the details about PARP eligibility:

1. PARP Inhibition as maintenance for patients with BRCA mutation

PARP inhibitors have traditionally been an effective treatment for women with ovarian cancer as maintenance therapy, which is treatment given after the initial surgery and chemotherapy nearly all women receive when diagnosed. During this phase, PARP inhibitors help maintain ovarian cancer in its depleted state following chemotherapy, extend the length of time before a new recurrence emerges, and sometimes even turn a temporary remission into a long-term cure.

According to Dr. Oliver Dorigo, a Gynecologic Oncologist at Stanford Medical School, this traditional approach shows that PARP inhibition is “particularly effective in those patients with BRCA mutations.” Tumor cells with these mutations have problems repairing DNA already, and the PARP inhibitors make that worse, causing cancer cells to die. Patients can either have the BRCA mutation in all the cells in their body, known as a germline mutation, or in just their tumor cells, known as a somatic mutation. Rucaparib and Olaparib, two of the three major PARP inhibitors, are currently approved for use as maintenance therapy for advanced/recurrent ovarian cancer patients with BRCA mutations. In other words, these two drugs are used for women who have undergone an initial surgery and multiple rounds of chemotherapy, but whose cancer continues to come back.

2. PARP Inhibition as maintenance therapy for all women

Once a woman’s cancer recurs, and if it has been at least 6 months since her last round of chemotherapy, she is usually treated again with a combination of platinum and a second drug.  If she demonstrates a response to this combination, she may be eligible for PARP inhibitor maintenance with either Niraparib, Rucaparib or Olaparib.

3. PARP Inhibition as initial therapy for patients with BRCA mutation

There is currently a clinical trial underway to test whether Olaparib can be used in ovarian cancer patients with BRCA mutation directly after just the first round of chemotherapy following surgery, rather than waiting until after several rounds, to prevent recurrence. The trial, known as the SOLO1 trial, has shown that women with BRCA mutations who receive Olaparib directly after initial surgery and one round of chemotherapy live up to two years longer than those who do not.

Thus, PARP inhibitors can be used as maintenance therapy in this setting to help maintain the response received from chemotherapy and extend the time to a first recurrence.  Some of these women have gone many years (3+) without having a recurrence at all and are still being followed. Currently Olaparib is the only drug indicated for this setting.

4. PARP Inhibition as the primary treatment after multiple recurrences in women with BRCA mutation

If a woman has a BRCA mutation and suffers a third recurrence (or even a fourth recurrence) she may be eligible for PARP inhibitor therapy as treatment, without having received chemotherapy first.

5. PARP Inhibition as initial therapy for all patients

There is another clinical trial, called the PRIMA trial, that is looking at whether Niraparib can be used in ovarian cancer patients directly after just the first round of chemotherapy following surgery, regardless of whether they have a BRCA mutation. Although the results are still not clear, it does appear that all women who receive Niraparib early on in treatment live longer than those who don’t.

Regardless of the situation, it is clear that PARP inhibitors may end up being an option for nearly all ovarian cancer patients. Be sure to discuss PARP inhibitors with your physician.

Learn more about the side effects of PARP inhibitors here.

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