The new class of ovarian cancer drugs called PARP inhibitors, which so far includes olaparib, rucaparib, and niraparib, is giving women—especially those with specific tumor makeups—an exciting sense of hope.
The Food and Drug Administration has approved niraparib (brand name ZEJULA) for almost all women regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what’s called front-line treatment. Most recently, 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.
“For the first time in the history of this field, and certainly for the first time for me, we’re actually using the ‘C’ word,” says Dr. Michael Birrer, Senior Scientist of the O’Neal Comprehensive Cancer Center at UAB. “We’re actually thinking maybe we’ve cured some of these patients—that’s how exciting it is.”
How PARP Inhibitors Work
Poly ADP ribose polymerase (PARP) inhibitor drugs work by preventing cancer cells that have been damaged—often during the course of chemotherapy treatment—from naturally healing. To accomplish this, and, in turn, effectively kill the cancer cell, the PARP-inhibitor drug blocks the necessary mechanism of repair, the PARP enzyme, which the cancer cell requires to fix single-strand breaks in its DNA.
PARPs for Maintenance
Because the drugs work by blocking damaged cells from healing, they’re usually used in the “maintenance” period of treatment, after a woman has already undergone chemotherapy and possibly surgery. When used as maintenance therapy, PARP inhibitors can potentially prevent recurrence and prolong remission—possibly forever.
Having said that, the effect a PARP inhibitor may have on your specific ovarian cancer will vary greatly depending on the specific genetic makeup of your tumor—making it necessary for your doctor to carefully choose the right time to prescribe one of these drugs.
“When a PARP is used would relate a lot to the characteristics of that specific tumor,” Dr. Birrer says.
PARPs for Women With BRCA Mutations
For some women, particularly those who carry a BRCA gene mutation like BRCA1 or BRCA2, PARP inhibitors may be used early on during treatment, perhaps directly after initial surgery or chemotherapy. For other women, the drugs might be prescribed down the line, after multiple rounds of chemotherapy, surgery, or other means of treatment.
PARPs and HRD
This difference in timing, Dr. Birrer explains, has to do with whether a woman’s cancer cells have a high degree of a characteristic called “homologous recombination deficiency” — which can come hand in hand with a BRCA mutation. Homologous recombination-deficient cells lack the ability to accomplish a specific type of DNA repair pathway on their own, which, in turn, makes them much more sensitive and responsive to PARP inhibitors.
“Who should get a PARP inhibitor is the fundamental question,” Dr. Birrer says, adding that, for many women diagnosed with ovarian cancer, the “when” is an equally pressing question.
Will You Benefit?
If your doctor does not bring up PARP inhibitors early-on during the course of your treatment, you should absolutely ask. Having this conversation could be vital to your long-term and progression-free survival, and unfortunately, only 50 percent of women today who are eligible for PARP inhibitors actually end up receiving them. Even this number may be a high estimate, as the rate of genetic testing is only 10% in all ovarian cancer patients, and we don’t know how many patients who aren’t tested might be eligible.
And with the promising outcomes for those treated with PARP inhibitors, which Dr. Birrer points out has shown a “flattening curve,” indicating progression-free survival in the median population of ovarian cancer patients, doctors are recognizing a huge curative potential for these new drugs.
Education and transparent provider-patient discussions about PARP-inhibitor eligibility, as well as the side effects and high prices associated with these drugs, can make a dramatic difference in treatment results. No two cancers are the same, and every patient has a different level of tolerance for side effects and financial burdens. So although PARP inhibitors are giving many women with ovarian cancer a tremendous amount of hope, they shouldn’t be universally prescribed.
Learn more about the side effects of PARP inhibitors here.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Michael Birrer is a Professor at the University of Alabama Birmingham. Read More
The new class of ovarian cancer drugs called PARP inhibitors, which so far includes olaparib, rucaparib, and niraparib, is giving women—especially those with specific tumor makeups—an exciting sense of hope.
The Food and Drug Administration has approved niraparib (brand name ZEJULA) for almost all women regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what’s called front-line treatment. Most recently, 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.
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“For the first time in the history of this field, and certainly for the first time for me, we’re actually using the ‘C’ word,” says
Dr. Michael Birrer, Senior Scientist of the O’Neal Comprehensive Cancer Center at UAB. “We’re actually thinking maybe we’ve cured some of these patients—that’s how exciting it is.”
How PARP Inhibitors Work
Poly ADP ribose polymerase (PARP) inhibitor drugs work by preventing cancer cells that have been damaged—often during the course of chemotherapy treatment—from naturally healing. To accomplish this, and, in turn, effectively kill the cancer cell, the PARP-inhibitor drug blocks the necessary mechanism of repair, the PARP enzyme, which the cancer cell requires to fix single-strand breaks in its DNA.
PARPs for Maintenance
Because the drugs work by blocking damaged cells from healing, they’re usually used in the “maintenance” period of treatment, after a woman has already undergone chemotherapy and possibly surgery. When used as maintenance therapy, PARP inhibitors can potentially prevent recurrence and prolong remission—possibly forever.
Having said that, the effect a PARP inhibitor may have on your specific ovarian cancer will vary greatly depending on the specific genetic makeup of your tumor—making it necessary for your doctor to carefully choose the right time to prescribe one of these drugs.
“When a PARP is used would relate a lot to the characteristics of that specific tumor,” Dr. Birrer says.
PARPs for Women With BRCA Mutations
For some women, particularly those who carry a BRCA gene mutation like BRCA1 or BRCA2, PARP inhibitors may be used early on during treatment, perhaps directly after initial surgery or chemotherapy. For other women, the drugs might be prescribed down the line, after multiple rounds of chemotherapy, surgery, or other means of treatment.
PARPs and HRD
This difference in timing, Dr. Birrer explains, has to do with whether a woman’s cancer cells have a high degree of a characteristic called “homologous recombination deficiency” — which can come hand in hand with a BRCA mutation. Homologous recombination-deficient cells lack the ability to accomplish a specific type of DNA repair pathway on their own, which, in turn, makes them much more sensitive and responsive to PARP inhibitors.
“Who should get a PARP inhibitor is the fundamental question,” Dr. Birrer says, adding that, for many women diagnosed with ovarian cancer, the “when” is an equally pressing question.
Will You Benefit?
If your doctor does not bring up PARP inhibitors early-on during the course of your treatment, you should absolutely ask. Having this conversation could be vital to your long-term and progression-free survival, and unfortunately, only 50 percent of women today who are eligible for PARP inhibitors actually end up receiving them. Even this number may be a high estimate, as the rate of genetic testing is only 10% in all ovarian cancer patients, and we don’t know how many patients who aren’t tested might be eligible.
And with the promising outcomes for those treated with PARP inhibitors, which Dr. Birrer points out has shown a “flattening curve,” indicating progression-free survival in the median population of ovarian cancer patients, doctors are recognizing a huge curative potential for these new drugs.
Education and transparent provider-patient discussions about PARP-inhibitor eligibility, as well as the side effects and high prices associated with these drugs, can make a dramatic difference in treatment results. No two cancers are the same, and every patient has a different level of tolerance for side effects and financial burdens. So although PARP inhibitors are giving many women with ovarian cancer a tremendous amount of hope, they shouldn’t be universally prescribed.
Learn more about the side effects of PARP inhibitors here.
Learn more about SurvivorNet's rigorous medical review process.
Dr. Michael Birrer is a Professor at the University of Alabama Birmingham. Read More
