PARP inhibitors are an exciting new wave of treatment for women with ovarian cancer. SurvivorNet’s extensive conversations with some of the top gynecologic oncologists in the country reveal that PARP inhibitors are rapidly becoming an integral part of comprehensive ovarian cancer treatment for an ever-growing number of women. Traditionally, these drugs have only been used in treatment for women who have a mutation in a gene, BRCA, which makes them susceptible to the genetic pathway which PARPs employ. As doctors find new applications for PARP inhibitors, however, the use of this class is only expanding,
These drugs have now been shown to be an effective treatment for women across the progression of ovarian cancer, from initial treatment to recurrence. Up until recently, PARP existed primarily as a treatment for ovarian cancer that had recurred and as a form of so-called maintenance therapy, which is given after an initial surgery and one or more rounds of chemotherapy. During this phase, PARP inhibitors help to maintain ovarian cancer in its depleted state following initial treatment, help to extend the length of time before a new recurrence emerges, and sometimes even help to turn a temporary remission into a long-term cure.
PARP inhibitors are available to almost all women, though women with BRCA gene mutations or who are HRD may benefit the most from these drugs. However, the American Society of Clinical Oncology (ASCO) released new 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.
How PARP Inhibitors Work
PARP inhibitors work by blocking an enzyme—known as PARP—used by cells to repair damage to their DNA. Without normally-functioning PARP, tumor cells will accumulate more and more DNA damage, and will eventually die.
PARP inhibitors interrupt the process of single stranded DNA repair, an essential part of cell replication. Defects in DNA repair ultimately cause cell death. PARP inhibitors work best when there is a second error in DNA repair, such as that caused by a mutation in BRCA. BRCA is a critical player in homologous recombination, a highly effective double stranded DNA repair process. BRCA is not the only important part of homologous recombination, other genes are involved. 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.
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.
Due to limited benefit in progression free survival seen in the absence of HRD, gynecologic oncologists differ on whether PARP inhibitors should be universally recommended in the “upfront maintenance setting.” Each patient should be made aware of risks and benefits to PARP inhibitor maintenance and decide with their oncologist what is the best treatment plan for them.
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.
Who Should Ask About PARP Inhibitors?
If you’ve been diagnosed with ovarian cancer, you should ask your physician about PARP inhibitors, says Dr. Oliver Dorigo, a Gynecologic Oncologist at Stanford Medical School. According to Dorigo, “We encourage all of our patients to bring up a discussion about PARP inhibitors with their physicians.”
Despite their clear effectiveness in the maintenance phase of ovarian cancer patients, only 50% of women eligible to receive PARP inhibitors do so, says Dr. Dorigo. He believes this may largely be due to a lack of information about the potential benefits of the treatments. “We need to educate our patients and our providers about the usefulness of these drugs,” asserts Dorigo.
Side Effects?
The different PARP inhibitors do have some varying side effects, which oncologists need to evaluate carefully. Some of these considerations are explained here.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Oliver Dorigo is a gynecologic oncologist at Stanford University Medical Center. Read More
PARP inhibitors are an exciting new wave of treatment for women with ovarian cancer. SurvivorNet’s extensive conversations with some of the top gynecologic oncologists in the country reveal that PARP inhibitors are rapidly becoming an integral part of comprehensive ovarian cancer treatment for an ever-growing number of women. Traditionally, these drugs have only been used in treatment for women who have a mutation in a gene, BRCA, which makes them susceptible to the genetic pathway which PARPs employ. As doctors find new applications for PARP inhibitors, however, the use of this class is only expanding,
These drugs have now been shown to be an effective treatment for women across the progression of ovarian cancer, from initial treatment to recurrence. Up until recently, PARP existed primarily as a treatment for ovarian cancer that had recurred and as a form of so-called maintenance therapy, which is given after an initial surgery and one or more rounds of chemotherapy. During this phase, PARP inhibitors help to maintain ovarian cancer in its depleted state following initial treatment, help to extend the length of time before a new recurrence emerges, and sometimes even help to turn a temporary remission into a long-term cure.
Read More PARP inhibitors are available to almost all women, though women with BRCA gene mutations or who are HRD may benefit the most from these drugs. However, the American Society of Clinical Oncology (ASCO) released
new 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.
How PARP Inhibitors Work
PARP inhibitors work by blocking an enzyme—known as PARP—used by cells to repair damage to their DNA. Without normally-functioning PARP, tumor cells will accumulate more and more DNA damage, and will eventually die.
PARP inhibitors interrupt the process of single stranded DNA repair, an essential part of cell replication. Defects in DNA repair ultimately cause cell death. PARP inhibitors work best when there is a second error in DNA repair, such as that caused by a mutation in BRCA. BRCA is a critical player in homologous recombination, a highly effective double stranded DNA repair process. BRCA is not the only important part of homologous recombination, other genes are involved. 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.
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.
Due to limited benefit in progression free survival seen in the absence of HRD, gynecologic oncologists differ on whether PARP inhibitors should be universally recommended in the “upfront maintenance setting.” Each patient should be made aware of risks and benefits to PARP inhibitor maintenance and decide with their oncologist what is the best treatment plan for them.
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.
Who Should Ask About PARP Inhibitors?
If you’ve been diagnosed with ovarian cancer, you should ask your physician about PARP inhibitors, says Dr. Oliver Dorigo, a Gynecologic Oncologist at Stanford Medical School. According to Dorigo, “We encourage all of our patients to bring up a discussion about PARP inhibitors with their physicians.”
Despite their clear effectiveness in the maintenance phase of ovarian cancer patients, only 50% of women eligible to receive PARP inhibitors do so, says Dr. Dorigo. He believes this may largely be due to a lack of information about the potential benefits of the treatments. “We need to educate our patients and our providers about the usefulness of these drugs,” asserts Dorigo.
Side Effects?
The different PARP inhibitors do have some varying side effects, which oncologists need to evaluate carefully. Some of these considerations are explained here.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Oliver Dorigo is a gynecologic oncologist at Stanford University Medical Center. Read More
