Understanding platinum-sensitive vs. platinum-resistant disease
- About 80 percent of ovarian cancer patients will go into remission after their initial treatment.
- Unfortunately, a majority of women may experience a cancer recurrence.
- Women with cancer that responds to chemotherapy for more than six months are considered platinum-sensitive.
- Platinum-sensitive patients may see more benefit from treatment with PARP inhibitor.
Many patients with ovarian cancer will respond to initial treatment with chemotherapy in that actually puts their disease into remission. Indeed about 80 percent of women will go into remission following chemotherapy and surgery. Unfortunately, many will experience a recurrence.Read More
Dr. Schilder says anybody with any type of cancer should consider a clinical trial even at the time of their initial diagnosis.
Using a PARP Inhibitor
Research has shown that patients who respond to platinum based chemotherapy in the upfront setting may benefit from maintenance treatment with a PARP inhibitor or the drug bevacizumab. PARP inhibitors help keep cancer cells from repairing their damaged DNA, making them more likely to die. They’re an oral medication you can take at home, so you don’t have to go to an infusion center or schedule visits with your physician to receive them.
While initially, women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, and then in what’s called maintenance therapy, newer research has shown that women with the BRCA gene mutation (and indeed almost all women), can consider using PARP inhibitors throughout their treatment.
Newly-Diagnosed Epithelial Ovarian Cancer
The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer irrespective of whether the tumor is HRD. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.
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.
Using PARPs To Treat Recurrence
Unfortunately, too often, ovarian cancer comes back.
For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Lynparza, Zejula and another PARP inhibitor called Rubraca (rucaparib) are FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.
For some women who have had prior chemotherapy treatments, Rubraca, Zejula or Lynparza may also be options. These uses are based on factors such as number of prior therapies and BRCA mutation or HRD.
The different PARP inhibitors do have some varying side effects, which oncologists need to evaluate carefully.
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 new understanding evolving around the use of PARP inhibition is a major reason why genetic testing is so important, and recommended to patients when they’re first diagnosed.
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