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PARP Inhibitors Have Potential to Benefit Larger Patient Populations in Ovarian Cancer

Gina Columbus @ginacolumbusonc
Published: Monday, Sep 18, 2017

Bhavana Pothuri, MD
Bhavana Pothuri, MD
The addition of 3 PARP inhibitors to the landscape of ovarian cancer—rucaparib (Rubraca), olaparib (Lynparza), and niraparib (Zejula)—have led to practice-changing, targeted treatment options for patients whose diseases progress on chemotherapy. The recent FDA approvals of olaparib and niraparib in the maintenance settings, specifically, have opened a new door where previously there were no such therapies available.

Now, clinical trials are testing PARP inhibitors in combination with immunotherapy to increase antitumor activity. Rucaparib is currently being explored in combination with atezolizumab (Tecentriq) in a phase Ib open-label study, with dose-finding and dose-expansion phases (NCT03101280). For the dose-expansion phase, patients must have a deleterious germline or somatic BRCA 1/2 mutation or tumors that are BRCA wild-type, but show high levels of loss of heterozygosity.

The ongoing confirmatory study for rucaparib’s approval, ARIEL4, is comparing rucaparib with chemotherapy in patients with BRCA-positive ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 2 prior platinum-based chemotherapy regimens (NCT02855944).

“Understanding that [PARP inhibitors are] another therapy in our armamentarium for the treatment of ovarian cancer is really important,” explained Bhavana Pothuri, MD, an associate professor in the Department of Obstetrics and Gynecology at NYU Langone's Perlmutter Cancer Center.

In an interview during the OncLive® State of the Science SummitTM on Treatment Options in Ovarian Cancer, Pothuri discussed the available PARP inhibitors and ongoing trials further investigating these agents in ovarian cancer.

OncLive: What did you discuss regarding PARP inhibitors in ovarian cancer?

Pothuri: It is a very exciting time for PARP inhibitors. The PARP inhibitors are a class of targeted agents that are utilized in ovarian cancer, and this is important because ovarian cancer accounts for only about 20% of gynecologic malignancies, but it accounts for over 50% of gynecologic cancer deaths. There is a real need for new agents, and the PARP inhibitors are a class of new agents for which we now have approvals with multiple different drugs.

It’s an exciting time. The first PARP inhibitor that has been approved was olaparib in December 2014. Olaparib was approved in patients with recurrent ovarian cancer who have had 3 or more prior lines of therapy, and were BRCA-mutation carriers. 

This was very exciting. About 2 years later, rucaparib, another PARP inhibitor, was also approved for 2 or more lines of prior treatment, and it was approved in patients with either a somatic or a germline mutation—so either a mutation in the tumor or in the blood. Again, that expanded the access a little bit and allowed us to use PARP inhibitors earlier in a patient’s disease course. Again, this is more progress for our patients with ovarian cancer. 

The recent approvals for maintenance [therapy] are also very exciting. The first PARP inhibitor to be approved was niraparib for maintenance therapy, and this was approved in patients with 2 or more lines of platinum therapy. Patients who responded had either a complete response or a partial response to prior platinum therapy. The data were impressive, and it looked like there was a benefit among all patients, regardless of BRCA mutation status. This led to approval in all patients with recurrent ovarian cancer who responded to prior platinum therapy.

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