The New Combination Treatment
- A two-drug-treatment combination was approved by the FDA as maintenance therapy for ovarian cancer.
- Maintenance therapy is intended to prolong cancer remission.
- The two drugs, olaparib (brand name LYNPARZA) and bevacizumab (brand name Avastin), each fight cancer in different ways.
How PARP Inhibitors Work
One of the key things to know about PARP inhibitors is that your genetic makeup and specific features of your cancer will have a significant impact on how effective these drugs may be. Experts tell SurvivorNet that every woman with ovarian cancer should get a genetic test to determine if they have a mutation called BRCA, because the mutation enables PARP inhibitors to function much more powerfully. Importantly, there is increasing data that even women without BRCA mutations can still derive some benefit from these drugs.
Read MoreStudy Finds Significant Benefit
The FDA based their May 2020 approval on a study done in Europe known as PAOLA-1, which looked at patients who received chemotherapy with bevacizumab, then continued the bevacizumab along with either a placebo or with olaparib. "The study put both together to try to see if there was a benefit"a difference in progression-free survival between the two groupssays Dr. Lynn Parker, gynecologic oncologist at Norton Cancer Institute in Louisville Kentucky. Findings suggest that for women with specific gene mutations or biomarkers there was a significant benefit with the combination therapy. "That was true in the population with BRCA mutations, whether it was an inherited mutation (called a germline mutation) or a mutation in the tumor (called a somatic mutation)," experts tell SurvivorNet."Looking at the data from that study it seems the group that most likely benefits the most from it are patients with homologous recombination deficiency,” says Dr. Parker. Homologous recombination deficiency, or HRD, is a genetic factor that indicates ovarian cancer cells cannot easily repair their own damaged genetic material.
Another important statistic from the clinical trial is called the hazard ratio, which quantifies the reduction in the risk of the disease recurring. In the PAOLA-1 trial, the hazard ratio in the population of women with either a BRCA mutation or HRD was about 0.3 or 0.4. Meaning they had a 60 to 70 percent reduced risk of the cancer returning when using this maintenance strategy. That’s exciting news for patients and their providers.
More Promising Options for Ovarian Cancer Patients
The approval of this new combination therapy comes on the heels of another recent approval in April 2020 for the PARP inhibitor, niraparib (brand name Zejula) as maintenance treatment for ovarian cancer. Initially, women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, but newer research indicated that almost all women can consider using this PARP inhibitor throughout their treatment. So patients now have options for maintenance therapy using niraparib or using olaparib plus bevacizumab. Olaparib is also approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.
In August 2020 the American Society of Clinical Oncology (ASCO) released 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.
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.
Weighing Treatment Benefits and Risks
PARP inhibitors, while a promising treatment, also carry risks. Dr. Amanika Kumar of the Mayo Clinic spoke to SurvivorNet and cautioned that women need to speak with their doctor to evaluate the benefit of taking a PARP inhibitor to prolong life because the drugs do have toxicities. Patients with HRD (homologous recombination deficiency) have a far better response than those without, and those with BRCA mutations even more so, Dr. Kumar says. Patients who have no mutation or HRD should think carefully about going on these meds.
Dr. Parker agrees. "I think if a patient is in a situation of choosing maintenance, then we need to have those discussions about the risk and the benefits of one option versus both drugs together. Just because something can be given, we [still] have to make sure that it’s as safe as possible, and that patients understand the risks and benefits."
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