Side Effects of PARP Inhibitors for Ovarian Cancer Patients

Three drugs in a class called PARP inhibitors are a welcome addition to the arsenal of medications available to treat ovarian cancer.

The three different PARP inhibitors were once largely prescribed only to patients who were in the advanced stages of the disease or who carried the BRCA mutation.  This is no longer the case, and now the drugs are potentially available to all eligible women with advanced stage or recurrent ovarian cancer. While initially, 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.

Which Drugs Are Approved?

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. The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process. Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.

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.

Says gynecologic oncologist Dr. Saketh Guntupalli, University of Colorado Denver, “PARP inhibitors are safe and can be an effective part of ovarian cancer treatment for more women at more stages of treatment than ever before.”

How Do PARP Inhibitors Work?

PARP inhibitors work by fighting the disease on a molecular level, preventing cancer cells from repairing their own genetic material. In addition to their effectiveness against ovarian cancer, PARP inhibitors are also convenient as they are administered in pill form and can be taken by patients at home, unlike most chemotherapy which is given through an intravenous line.

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.”

The side effects of PARP inhibitors can be severe in some patients, and doctors have to closely monitor patients taking these drugs.

Risks and Benefits Must Be Discussed On An Individual Basis

The three PARP inhibitor drugs available–niraparib, rucaparib, and olaparib — each carries its own set of risks and benefits, so it’s important to discuss what’s right for you with your medical team.

Some fairly common side effects of all PARP inhibitors include stomach upset, nausea and vomiting, diarrhea and/or constipation. Reflux or heartburn may be remedied with antacid or a proton pump inhibitor your doctor can prescribe as needed. Anti-nausea medications are also effective.

Another side effect of these drugs is a decrease in the bone marrow’s ability to produce red and white blood cells. To combat anemia, your oncologist may prescribe iron, blood transfusions, or a stimulant agent such as Ritalin to help with fatigue. Lowered blood platelet production can lead to excessive bleeding. “That’s something that we need to watch very, very closely,” says Dr. Guntupalli, “because you need to be able to make a clot if you have a cut somewhere on your body.” A very small percentage of patients may develop a rare disorder known as Myelodysplastic Syndrome, or extreme inhibition of the cell lines that make red and white blood cells.

In addition to these side effects common to all of the PARP inhibitors, the three drugs now available carry their own specific risks. Niraparib, for example, may cause heart palpitations and a rapid heart rate (tachycardia). Rucaparib and olaparib may affect the liver and kidneys. “So if you have a patient that has a longstanding history of drinking or has a hepatitis infection you might not want to use that drug,” says Dr. Guntupalli. “It can cause the liver enzymes to go up and cause inflammation of the liver.”

For patients who are able to avoid severe side effects and can tolerate continued use of these drugs, the medical team works to control milder side effects in two ways: by adjusting dosage up or down according to the individual patient’s needs, and by prescribing medications that relieve nausea, gastrointestinal issues, or fatigue when those symptoms occur. “We try to dose adjust so we start high and then we dose reduce to help mitigate some of those side effects,” Dr. Guntupalli explains. “We’ve had patients who have had very exaggerated responses, or responses that have caused them to have lots of toxicity,” says Dr. Guntupalli.  But, he adds,  “those cases are few and far between.”

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