PARP Inhibitors: Balance the Benefits With Risks
- New guidelines recommend PARP inhibitors for women with newly diagnosed stage III or IV epithelial ovarian cancer who have improved with chemotherapy.
- These drugs can help women with and without genetic mutations.
- Women need to balance benefits of these drugs against side effects such as nausea, vomiting, and fatigue.
PARP inhibitors are drugs that prevent cancer cells from repairing their damaged DNA. The first of these drugs were approved only for women with BRCA1 and BRCA2 gene mutations, but since then, the approvals have broadened, so that even women who don’t have genetic mutations can benefit from them. “In the past three years, we have seen a remarkable expansion of the role of PARP inhibitors in the management of women with epithelial ovarian cancers,” Dr. Stephanie Wethington, gynecologic oncologist at Johns Hopkins Medicine, tells SurvivorNet.
Read More“We now understand that PARP inhibitors are a crucial tool in our armamentarium for the initial treatment of this disease. They are affording patients longer periods without disease recurrence, and may indeed be increasing rates of cure,” Dr. Jocelyn S. Chapman, a gynecologic oncologist at UCSF, tells SurvivorNet.
The Science Behind PARP Inhibitors
PARP inhibitors’ ability to treat ovarian cancer stems from their effects on DNA repair. “DNA damage is occurring in our cells every day,” Dr. Marta Crispens, gynecologic oncologist at Vanderbilt University Medical Center tells SurvivorNet. “Fortunately, our cells have elaborate systems for repairing that damage.”
PARP is the protein our bodies use to repair broken strands of DNA so that cells can survive. This same protein also helps cancer cells repair themselves. PARP inhibitors block the pathway that allows cancer cells to fix their DNA, leading to their untimely death.
These drugs work particularly well in women with BRCA gene mutations. BRCA is also involved in DNA repair, and when it’s damaged, or mutated, cancer cells become even more vulnerable to the effects of PARP inhibitors. “The cancer cells will not be able to effectively repair DNA damage, which will build up and cause the death of the cancer cell,” Dr. Crispens says.
Dr. Kellie Schneider, gynecologic oncologist at Novant Health, explains how PARP inhibitors treat ovarian cancer
Homologous recombination deficiency (HRD) is another Achilles’ heel in the cancer cells’ ability to repair themselves, which is why women with this genetic factor also respond better to PARP inhibitors. Doctors can test for BRCA genes and HRD when women are first diagnosed, to help guide their treatment.
Related: What Genetic Testing Can Reveal About Ovarian Cancer
The benefit of maintenance therapy can differ from one woman to another, Dr. Kimberly Levinson, gynecologic oncologist at Johns Hopkins University, tells SurvivorNet. For example, she says PARP inhibitors extend progression-free survival by about 11 months in women with both BRCA mutations and HRD, but only about three months in those without HRD. Also keep in mind that these numbers don’t indicate how long women with this cancer live — only how much time they have before their cancer returns.
Are PARP Inhibitors Worth the Risks?
For any cancer treatment, women need to balance benefits against the risks of side effects, which for PARP inhibitors can include nausea, vomiting, reduced white blood cell counts, and fatigue. Each PARP inhibitor has its own unique side effects, as well.
Some women may find that a survival increase of two-and-a-half months is worth any nausea or fatigue they might have during that time, Dr. Levinson says. “For others, it may be more important to feel well.”
Dr. David Engle of Baptist Medical Group offers advice on how to manage PARP inhibitor side effects
What’s more, PARP inhibitors can be costly — $14,700 per month by one estimate. “Given the variable benefit, as well as the potential physical and financial toxicity of these agents, the choice for maintenance therapy should be individualized,” Dr. Crispens says.
Related: Side Effects of PARP Inhibitors
Should You Get PARP Inhibitors?
The new ASCO guidelines recommend that women should be “offered” PARP inhibitors, not that they should definitely receive them. Ultimately, whether to get these drugs should be based on a woman’s unique risk factors and preferences. Dr. Levinson encourages women to “openly discuss the risks and benefits of this treatment with their physician in order to make the best decision for them.”
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