Examining PARP Inhibitors in the Maintenance Setting of Ovarian Cancer

PARP inhibitors have drastically changed the treatment landscape — and outcomes – of patients with ovarian cancer. However, despite promise shown among this class of drugs, it is still unclear which agent is the best to use in the maintenance setting.

At the 2018 Society of Gynecologic Oncology Annual Winter Meeting, David O'Malley, M.D., assistant professor in the Department of Obstetrics and Gynecology at The Ohio State University Comprehensive Cancer Center, discussed the various PARP inhibitors available and offered background on the debate of which to use.

“Currently, there are two drugs that are approved, and we think there will be a third drug. Looking at those drugs and trying to figure out what to use is not yet possible,” O’Malley said in an interview with OncLive, a sister publication of CURE.

The two PARP inhibitors that are currently approved in the maintenance setting for ovarian cancer are Lynparza (olaparib) and Zejula (niraparib).

Not far behind those two drugs is Rubraca (rucaparib), another PARP inhibitor that improved progression-free survival (PFS) in the maintenance setting for patients with platinum-sensitive, high-grade ovarian, fallopian tube, or primary peritoneal cancer, according to results from the phase 3 ARIEL3 trial.

“I do not think those drugs will ever be compared. They all seem to have similar efficacy, and a lot of this comes down to balancing toxicity, dosing schedules, convenience, and other factors,” O’Malley said.

Lynparza is approved for two indications in ovarian cancer treatment: one for maintenance therapy regardless of BRCA mutation status, and another for when the patient has a BRCA mutation and has had three or more prior lines of therapy.

For Rubraca, the maintenance approval is for patients who have had at least two lines of therapy and have a BRCA mutation. Both drugs are approved for platinum-sensitive patients, many of whom have a BRCA mutation.

There are also some combinations being looked at for the maintenance setting, such as Zejula plus Avastin (bevacizumab) and cediranib plus Lynparza — both of these combination therapies are being looked at in ongoing phase 3 clinical trials.

“We do not have the results on this and we are hoping to enroll patients in those trials,” O’Malley said. “Since there are so many clinical trials out there, we hope to have any eligible patient treated on a clinical trial.”

Regardless of what PARP inhibitor regimen a patient is assigned, toxicities that come along with these drugs still pose some challenges. PARP inhibitors are usually well tolerated, but there can be some cases of fatigue, as well as gastrointestinal and hematologic events that can impact a patient’s quality of life.

“There are clearly side effects that we need to balance, and we need to look at patient-reported outcomes as we move forward in trying to ascertain the best place to use these drugs,” O’Malley said.