PARP Inhibitors Offer Promise, But ‘Pills Have Side Effects, Too’

PARP inhibitors are available to almost all women, though women with BRCA gene mutations or who are HRD proficient may benefit the most from these drugs.

However, 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.

PARP inhibitors, which are taken orally, work by preventing cancer cells from repairing their damaged DNA, causing them to die off rather than continue to spread.

"Because they’re pills, sometimes (patients) think, ‘Well, we just take the pill, we go about our day, we don’t have to think or worry about anything versus chemotherapy, (where) I had to come to the infusion center and receive a treatment, and that kind of infused chemotherapy is toxic,” says Dr. Eskander.

"But the reality is, PARP inhibitors are antineoplastic drugs, they’re anti-cancer drugs like other chemotherapy,” explains Dr. Eskander. “The intent is for them to continue to be effective at preventing the cancer from coming back, or potentially treating the cancer in some indications." And like other chemotherapy drugs, PARP inhibitors have side effects.

It’s important for providers to communicate with their patients taking PARP inhibitors, to continue seeing them in office even though they’re taking an oral pill rather than going to an infusion center for an intravenous treatment.

PARP Inhibitor Side Effects

PARP inhibitors have a few of what are called class-related side effects, and these are common to all three PARP inhibitor drugs approved to treat ovarian cancer.

• Fatigue is one of the most common side effects that patients experience when they start on an oral PARP inhibitor.
• Gastrointestinal, or GI side effects, are also common. They can include nausea, constipation or diarrhea, perhaps indigestion. The severity of the side effects vary: some patients may experience very little to none of the GI side effects while others may have more pronounced symptoms.
• The drug also affects the bone marrow, which in turn affects  white blood cells, red blood cells, and platelet counts.

In general, these are the "buckets" of side effects. However, “not all PARP inhibitors are created equal when it comes to side effects,” explains Dr. Eskander. “Some PARP inhibitors can cause a more pronounced drop in the platelets, for example, while others may cause more anemia, a drop in the red blood cell count. Some PARP inhibitors can cause an elevation in the blood pressure, which is unique.”

The drugs are not identical, and “the beauty of having several to choose from is that we can start with one PARP inhibitor, and if a patient is experiencing a particular side effect that we can't get beyond by interrupting (treatment) for a little bit or by reducing the dose, then I can stop that one and maybe try another PARP inhibitor to see if my patient will tolerate that (one better)."

Dr. Eskander says there are some rare, potentially life threatening but very uncommon side effects with PARP inhibitors. “One is AML, acute myelogenous leukemia (cancer of the blood and bone marrow), or MDS, myelodysplastic syndrome, (a group of disorders caused by poorly formed blood cells). They’re exceedingly rare, and the reality is we don’t exactly know what the relationship is of PARP inhibitors to that side effect."

Since many women with advanced ovarian cancer typically will have a recurrence, and no cure has yet been found, PARP inhibitors are offering women a new treatment that may potentially extend their survival time.

But as with all drugs, PARP inhibitors carry their own own set of risks and benefits, so it's important to talk with your healthcare team to see what type of treatment is right for you.

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."

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