PARP Inhibitors And Ovarian Cancer
- PARP inhibitors are now available to almost all women with ovarian cancer, even those without genetic mutations.
- These drugs respond best to BRCA1 and BRCA2 gene mutations, and these mutations are discovered through genetic testing.
- Researchers are still studying PARP inhibitors to see if they have additional benefits for women, and whether they would be useful in combination with other drugs.
The creation of PARP inhibitors marks a huge step in ovarian cancer treatment, specifically for women whose disease has returned. While PARP inhibitors are available to almost all women, women with BRCA gene mutations or whose tumors harbor HRD may benefit the most from these drugs. (The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.)
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.
What is a PARP inhibitor?
PARP inhibitors are a targeted therapy. They target a protein within cells known as PARP. PARP repairs damaged DNA within cells — inhibiting this repair mechanism in cancer cells means they can no longer repair their DNA, causing them to die.
“Initially, we started using PARP inhibitors in the recurrent setting, and then it became more in consideration for preventative treatment and now it is available for frontline therapy as well,” says Dr. Nabila Rasool, a gynecologic oncologist at Ascension Providence Hospital in Michigan.
How do you know if you are a good candidate for a PARP inhibitor?
Ideally, ovarian cancer patients will undergo genetic testing to look for genetic mutations such as BRCA 1 or BRCA 2 positivity that are an indication that PARP inhibitors might be more effective for you. If you’re not found to have a hereditary mutation, genetic testing on the tumors specifically is usually carried out, as they could have still have the DNA defects that inform treatment decisions, even if they’re not in the rest of your body.
Some PARP inhibitors might have additional benefits if used in a combination with other drugs. Lynparza is 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.
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.”
Learn more about SurvivorNet's rigorous medical review process.
Dr. Nabila Rasool is a board certified gynecologic oncologist at Ascension Providence Hospital - Southfield in Michigan. Read More
PARP Inhibitors And Ovarian Cancer
- PARP inhibitors are now available to almost all women with ovarian cancer, even those without genetic mutations.
- These drugs respond best to BRCA1 and BRCA2 gene mutations, and these mutations are discovered through genetic testing.
- Researchers are still studying PARP inhibitors to see if they have additional benefits for women, and whether they would be useful in combination with other drugs.
The creation of PARP inhibitors marks a huge step in ovarian cancer treatment, specifically for women whose disease has returned. While PARP inhibitors are available to almost all women, women with BRCA gene mutations or whose tumors harbor HRD may benefit the most from these drugs. (The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.)
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.
What is a PARP inhibitor?
Read More PARP inhibitors are a targeted therapy. They target a protein within cells known as PARP. PARP repairs damaged DNA within cells — inhibiting this repair mechanism in cancer cells means they can no longer repair their DNA, causing them to die.
“Initially, we started using PARP inhibitors in the recurrent setting, and then it became more in consideration for preventative treatment and now it is available for frontline therapy as well,” says Dr. Nabila Rasool, a gynecologic oncologist at Ascension Providence Hospital in Michigan.
How do you know if you are a good candidate for a PARP inhibitor?
Ideally, ovarian cancer patients will undergo genetic testing to look for genetic mutations such as BRCA 1 or BRCA 2 positivity that are an indication that PARP inhibitors might be more effective for you. If you’re not found to have a hereditary mutation, genetic testing on the tumors specifically is usually carried out, as they could have still have the DNA defects that inform treatment decisions, even if they’re not in the rest of your body.
Some PARP inhibitors might have additional benefits if used in a combination with other drugs. Lynparza is 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.
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.”
Learn more about SurvivorNet's rigorous medical review process.
Dr. Nabila Rasool is a board certified gynecologic oncologist at Ascension Providence Hospital - Southfield in Michigan. Read More
