Facts about PARP Inhibitors
- PARP inhibitors are a fairly new class of drugs providing hope for some ovarian cancer patients.
- Initially used only for women with a BRCA gene mutation or advanced disease, PARP inhibitors can now be offered to almost all women with ovarian cancer starting as part of an initial course of maintenance therapy after surgery and chemotherapy.
- Side effects of PARP inhibitors can be challenging. These medications are taken in pill form rather than through an intravenous line.
These drugs can be given both in early and later phases of cancer treatment, on their own or in concert with other chemotherapy drugs. All three types of PARP inhibitor drugs are administered orally, and women can take the pills at home or in a care setting after discussion with their medical team and a review of the drugs’ risks and benefits.
Read MoreWho Can Take PARP Inhibitors?
Whether you should consider a PARP inhibitor will likely be determined by a number of factors: the specific genetic make-up of your cancer, your disease stage, whether your cancer had a positive response to a so-called platinum based chemotherapy and your ability to tolerate the drug’s side effects. "PARP inhibitors have revolutionized our treatment of ovarian cancer," says gynecologic oncologist Dr. Saketh Guntupalli of the University of Colorado/Denver. Even though PARP inhibitors are now approved for almost all ovarian cancer patients, their effect is far greater in patients who have BRCA genetic mutations and something called homologous recombination deficiency (HRD). HRD means that a woman's ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to fight.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.
How PARP Inhibitors Work
PARP inhibitors target a specific enzyme and compromise cancer cells’ ability to repair themselves and replicate. Patients with ovarian cancer who stand to benefit the most from PARP inhibitors carry the BRCA mutation which is associated with ovarian cancer as well as breast cancer. However while women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, newer research has shown that women with the BRCA gene mutation (and indeed almost all women), can consider using PARP inhibitors throughout their treatment. The Food and Drug Administration has approved Zejula (niraparib) for almost all women regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what's called front-line treatment.
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.
However, 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."
Originally prescribed after a cancer has come back in women with BRCA mutations, PARP inhibitors can now be offered after initial surgery and chemotherapy, and continued for months, or even years, as long as the side effects are tolerated. The option to offer these drugs to women even after their first course of a different treatment increases the number of patients who can benefit. PARP inhibitors can also be used to help suppress recurrence of the disease. Again, the decision making process here will vary greatly among women, and will likely include the potential benefit the drugs can have (based again on genetics and molecular information unique to you).
PARP Inhibitors at Home
One advantage to taking PARP inhibitors is their convenience, a term not often associated with the fight against cancer. "They're pills, so patients don't have to spend hours and hours in a chemotherapy infusion center," Dr. Guntupalli explains. "You take them at home. Oftentimes, with telemedicine, we're able to follow patients from afar, without them having to come in to the office. I keep patients on them as long as they can tolerate it. Generally, at about two years, we would consider taking the patient off because it's an expensive drug and they do have side effects.”
The ability to use state-of-the-art cancer treatment at home, rather than having to report to a hospital or medical office for intravenous chemotherapy, is especially beneficial during the COVID-19 pandemic as cancer patients seek to reduce their chances of being exposed to the new coronavirus.
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