Who is Eligible for Niraparib (Zejula) Therapy?
- Niraparib (Zejula) is a PARP inhibitor that prevents cancer cells from repairing their damaged DNA.
- In the past, PARP inhibitors were mainly used to treat women with BRCA gene mutations.
- The recent FDA approval of Zejula extends to almost all patients, whether or not they have a BRCA gene mutation, who show a response to platinum-based chemotherapy.
- Response is much greater in women who carry a BRCA mutation or have positive homologous recombination deficiency (HRD) status
Poly (ADP-ribose) polymerase inhibitors, better known as PARP inhibitors, are a newer group of drugs that target an important enzyme involved in DNA repair. In other words, they kill cancer cells by preventing them from repairing their damaged DNA.
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Past studies of PARP inhibitors focused on women with mutations in the BRCA1 and BRCA2 genes, which help repair damaged DNA. These inherited mutations both increase the risk for ovarian cancer, and affect a woman’s response to cancer treatment. A recent clinical trial called PRIMA trial looked at the use of niraparib in a different population of women with ovarian cancer."They took a different tactic and looked at what we refer to as HRD-positive patients, who have a homologous recombination deficiency gene," says Dr. Engle. "That’s a much broader group of patients."
HRD is a genetic factor that is found in women who also have BRCA1 and 2 mutations, but can be found in other women as well. The presence of HRD means that the cancer cells have difficulty repairing themselves, which can make treatment with PARP inhibitors more effective. Women with ovarian cancer who have HRD respond better to platinum-based chemotherapy, as well as to PARP inhibitors. In fact, recent studies have shown that the presence of a BRCA mutation or HRD is predictive of a much stronger response to niraparib.
Expanding the indication for PARP inhibitors to include women with HRD means that many more patients with ovarian cancer can be treated with them.
"BRCA mutations account for approximately 20 to 25 percent of patients, while HRD may account for up to 50 percent of ovarian cancers," says Dr. Engle.
The PRIMA trial looked at using niraparib as first-line maintenance therapy. Women in the study were treated with niraparib after first having surgery for their cancer, and then receiving six cycles of a platinum-based chemotherapy. Women who responded well to this treatment were then given genetic tests to determine if they had a BRCA mutation or HRD. If they were an HRD patient, they then qualified to receive niraparib as a maintenance therapy, once they completed their chemotherapy regimen.
The American Society of Clinical Oncology (ASCO) released guidelines recommending 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.
More specifically, Zejula has been approved by the FDA for all women with newly-diagnosed ovarian cancer regardless of HRD or BRCA status. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer. For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Zejula is also FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.
Positive News for Ovarian Cancer Patients
The goal of the study was to improve progression-free survival, which means extending the period of time before the cancer comes back. Zejula increased the length of time to recurrence by 22 months, compared to 10 months in those who did not take it, says Dr. Engle. In other words, many women taking niraparib had an extra year cancer-free.
That is huge news to patients, says Dr. Engle, because it includes up to half of all women with ovarian cancer a much larger group than only those with BRCA mutations.
Women who’ve responded well to chemotherapy may want to talk to their doctor about trying niraparib as maintenance therapy since this new drug may keep cancer at bay for longer.
Dr. Amanika Kumar of The Mayo Clinic who spoke to SurvivorNet, cautioned that women still need to speak with their doctor to evaluate the benefit of taking a PARP inhibitor to extend life, because there are very real side effects due to the toxicity of the drug.
"Patients with HRD (homologous recombination deficiency) have a far better response than those without and those with BRCA mutations even more so. It is on us as clinicians to help patients understand the risks and benefits of treatment. Patients that have no mutation or HRD may choose not to go on maintenance (in fact I recommend they don't) because there is real toxicity to these meds."
Your doctor, patient education, and counseling can help you make decisions about cancer treatment, including PARP inhibitors like niraparib. Learning more about the drug can help you understand your individual risks and benefits, given your own genetic profile and the disease you're dealing with.
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