PARP Inhibitor Basics
- Women with BRCA mutations benefit the most from PARP inhibitors.
- Women with HRD tumors may also respond well.
- Women without a BRCA mutation have also been shown to benefit from PARP inhibitor therapy.
PARP inhibitors are a targeted therapy. They target a protein within cells known as PARP which repairs damaged DNA within those cells. Inhibiting this repair mechanism means cancer cells can no longer repair their DNA, causing them to die.
PARP inhibitors are now important as ovarian cancer maintenance therapy because they can prolong the time before cancer recurrence. “We don’t have overall survivor data yet since it’s too early for that but we know that there is a huge prolongation, about 40-plus months in the time until the cancer comes back,” says Dr. Marta Crispens, a gynecologic oncologist at Vanderbilt Health.
How Do PARP Inhibitors Work?
PARP inhibitors seem most effective in women who carry at BRCA 1 or 2 gene mutation, and this fact helps doctors understand more about how this new class of drugs works. BRCA 1 and 2 are DNA damage repair genes.
When a patient has a mutation in either of these genes, they can’t effectively repair DNA damage in the usual way, although the body has additional mechanisms to provide this function.
“The PARP inhibitors inhibit the back up methods so the cancer cell that is accumulating the DNA damage cannot fix the damage, the DNA damage accumulates, and the cell dies,” explains Dr. Crispens.
Who Can Take PARP Inhibitors?
While it was first established that women with a BRCA mutation responded well to PARP inhibitors, newer research has shown that women without the mutation — and, in fact, almost all women with advanced ovarian cancer — can consider using PARP inhibitors throughout their treatment. There are now three PARP inhibitors that have been FDA-approved for ovarian cancer treatment.
- 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.
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.
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.”
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.
Homologous Recombination Deficiency
What is HRD? It’s a genetic factor, sometimes present in women who also have mutations in the BRCA gene. HRD means that a woman’s ovarian cancer cells have trouble repairing themselves, which can make them easier to destroy.
Ovarian cancer patients with HRD exhibit specific clinical behaviors and improved responses to treatments with platinum-based chemotherapy and PARP inhibitors, according to researchers. This means that women with either the BRCA gene or HRD (or both) may benefit more from chemotherapy drugs and PARP inhibitors.
Learn more about SurvivorNet's rigorous medical review process.
Marta A. Crispens, MD, is director, division of gynecologic oncology at Vanderbilt University Medical Center. Read More
PARP Inhibitor Basics
- Women with BRCA mutations benefit the most from PARP inhibitors.
- Women with HRD tumors may also respond well.
- Women without a BRCA mutation have also been shown to benefit from PARP inhibitor therapy.
are a targeted therapy. They target a protein within cells known as PARP which repairs damaged DNA within those cells. Inhibiting this repair mechanism means cancer cells can no longer repair their DNA, causing them to die.
PARP inhibitors are now important as ovarian cancer maintenance therapy because they can prolong the time before cancer recurrence. “We don’t have overall survivor data yet since it’s too early for that but we know that there is a huge prolongation, about 40-plus months in the time until the cancer comes back,” says Dr. Marta Crispens, a gynecologic oncologist at Vanderbilt Health.
How Do PARP Inhibitors Work?
Read More PARP inhibitors seem most effective in women who carry at BRCA 1 or 2 gene mutation, and this fact helps doctors understand more about how this new class of drugs works. BRCA 1 and 2 are DNA damage repair genes.
When a patient has a mutation in either of these genes, they can’t effectively repair DNA damage in the usual way, although the body has additional mechanisms to provide this function.
“The PARP inhibitors inhibit the back up methods so the cancer cell that is accumulating the DNA damage cannot fix the damage, the DNA damage accumulates, and the cell dies,” explains Dr. Crispens.
Who Can Take PARP Inhibitors?
While it was first established that women with a BRCA mutation responded well to PARP inhibitors, newer research has shown that women without the mutation — and, in fact, almost all women with advanced ovarian cancer — can consider using PARP inhibitors throughout their treatment. There are now three PARP inhibitors that have been FDA-approved for ovarian cancer treatment.
- 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.
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.
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.”
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.
Homologous Recombination Deficiency
What is HRD? It’s a genetic factor, sometimes present in women who also have mutations in the BRCA gene. HRD means that a woman’s ovarian cancer cells have trouble repairing themselves, which can make them easier to destroy.
Ovarian cancer patients with HRD exhibit specific clinical behaviors and improved responses to treatments with platinum-based chemotherapy and PARP inhibitors, according to researchers. This means that women with either the BRCA gene or HRD (or both) may benefit more from chemotherapy drugs and PARP inhibitors.
Learn more about SurvivorNet's rigorous medical review process.
Marta A. Crispens, MD, is director, division of gynecologic oncology at Vanderbilt University Medical Center. Read More
