Women with Recurrent Ovarian Cancer Are Living Longer on PARP Inhibitors

Oncologists are committed to finding better ways to prolong life expectancies for the 250,000 women diagnosed with ovarian cancer worldwide each year. And for some of these women, PARP inhibitors are providing hope and extending life.

Using PARP Inhibitors To Treat Recurrence

1. 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. (A note about HRD: This is a genetic factor, sometimes present in women who have mutations in the BRCA gene. HRD means that a woman’s ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to fight. Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and PARP inhibitors, according to researchers.)
2. 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.

You Might Want To Understand Some Important Research to Back Up PARP Use For Ovarian Cancer Recurrence

In a clinical experiment known as the NOVA trial, the results of which were published in the December 2016 New England Journal of Medicine, women with ovarian cancer who took a PARP inhibitor were in remission significantly longer than those who did not use the medication. We spoke to Dr. Ursula Matulonis, chief of Gynecologic Oncology at the Dana Farber Cancer Institute, about the trial and its compelling results.

Dr. Matulonis says this trial’s results have profound applications. “It looked at a very large population of women, so really we need to continue to think about new ways of prolonging their lives even more,” Dr. Matulonis says.

The trial primarily looked at three groups:

• Patients with germline BRCA mutations.
• Patients who are HRD Positive (Homologous Recombination Deficiency, or some cells being unable to repair their DNA).
• Patients without inherited BRCA mutation.

Specifically, the NOVA trial showed that the PARP inhibitor called Niraparib (Zejula) kept cancer in remission longer in patients who:

Here’s the important part: In all three groups, patients who took Niraparib after receiving chemotherapy lived significantly longer than those who did not.

If you’re interested in the nitty gritty on the three groups:

1. Patients with germline BRCA mutations. Women with BRCA mutations are particularly susceptible to PARP inhibitors. Tumor cells with these mutations have problems repairing DNA already, and the PARP inhibitors lessen their effectiveness further, eventually causing these cancer cells to die. Women 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. The women in the NOVA trial had germline BRCA mutations, which are present in only 14 percent of women worldwide. In this trial, Niraparib kept cancer in remission longest for these women.
2. Patients who are HRD Positive. As we said above, women who are HRD (Homologous Recombination Deficiency) positive have mutations that make it more difficult for cancerous cells to perform a specific kind of DNA repair. Women with BRCA mutations fall into this broad category. Tumor cells with these mutations also have problems repairing DNA already, and the PARP inhibitors can further impede their ability to multiply, causing the cancerous cells to die. About 41-50 percent of patients are HRD positive, which means they have at least some of this factor in their cells. While not as susceptible to PARP inhibitors as women with BRCA mutations, Niraparib still kept cancer in remission significantly longer for HRD positive women in the trial.
3. Patients without inherited BRCA mutation. These women had no mutations affecting DNA repair. Nonetheless, these women with ovarian cancer who took Niraparib were in remission longer than those who did not.

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