What Are The Side Effects Of PARP Inhibitors For Ovarian Cancer Patients?

In their relatively short history, PARP inhibitors have been given to patients who have a BRCA-1 or BRCA-2 gene mutation. These drugs are most effective at stopping the growth of cancer when BRCA mutations are present. PARPs work by preventing damaged DNA from replicating into more cancer cells.

According to Dr. Fauci, patients may experience gastrointestinal (GI) symptoms, and unfortunately there are few ways doctors can prevent that side effect from occurring. However, doctors will adjust drug doses while monitoring GI symptoms and less than 20 percent of patients experience severe symptoms.

Another side effect patients may experience is anemia, which will be monitored by doctors. In some cases, patients will receive blood transfusions in order to address low hemoglobin counts in order to continue treatment. Luckily, Dr. Fauci says these side effects usually improve within the first one or two months of starting treatment, and it’s not uncommon for women to need PARP inhibitor dose adjustments during treatment.

“I always try to warn patients that dropping the dose does not mean we’re dropping the efficacy,” Dr. Fauci says. “It just means we have to find the dose that’s right for their body. Up to 30 to 50% of patients will require a dose reduction at some point.”

PARP Inhibitors Giving Hope To Cancer Patients

PARP inhibitors have been available for a few years, but the pool of patients who are eligible to use them has been expanding tremendously. Studies have shown that these drugs improved outcomes for all types of patients: women who are BRCA positive, those with homologous recombination deficiency (HRD), and even those who are BRCA negative.

HRD 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.

The American Society of Clinical Oncology (ASCO) released new 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.

Newly Expanded Use for PARP

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 indicated that women with the BRCA gene mutation (and indeed almost all women), can consider using PARP inhibitors even from the beginning of their treatment.

The Food and Drug Administration approved niraparib (brand name ZEJULA) 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.

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." Not all physicians with whom SurvivorNet spoke agree entirely with this recommendation, but all specialists stress how important it is to seek guidance from your physician and make decisions based on your personal circumstance.

With FDA approval, more health insurance companies are covering the considerable cost of the these drugs than in the past. If a patient is unable to get covered, there are programs offered through the drug manufactures where women can apply on behalf of patients.

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