Ursula A. Matulonis, MD
At the close of 2016, the FDA approved the PARP inhibitor rucaparib (Rubraca) for the treatment of patients with BRCA
-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy. Rucaparib was the second PARP inhibitor approved in the field, following the 2014 approval of olaparib (Lynparza) for the treatment of women with BRCA
-positive advanced ovarian cancer following 3 or more prior lines of chemotherapy.
These agents were recently joined by the PARP inhibitor niraparib (Zejula), which was just approved in March for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, regardless of BRCA
mutation status. This approval was based on the phase III NOVA trial, where niraparib reduced the risk of progression or death by 74% compared with placebo in patients with germline BRCA-
positive, platinum-sensitive, recurrent ovarian cancer.1,2
Shortly thereafter, olaparib was granted a priority review as a maintenance therapy in ovarian cancer. In the phase III SOLO-2 trial, maintenance olaparib showed a 70% reduction in the risk of progression or death versus placebo in patients with platinum-sensitive, relapsed, BRCA
-mutant ovarian cancer.
“It is exciting in that there are now options for the patients, but also that more research is being done on ovarian cancer and more drugs are being approved,” said Ursula A. Matulonis, MD, a senior author on the NOVA trial, and director, Gynecologic Oncology, Dana-Farber Cancer Institute, professor of Medicine, Harvard Medical School.
Agents with broader labels, such as niraparib, are a particularly meaningful advancement, adds Matulonis. Niraparib—unlike olaparib and rucaparib—does not require patients to have a BRCA
mutation, allowing for a wider range of women to be treated.
In an interview with OncLive,
Matulonis discussed the latest regulatory advances with PARP inhibitors and their continued growth in the treatment of patients with ovarian cancer.OncLive: Can you provide an overview of the data that led to the approval of niraparib?Matulonis
: This was data from a phase III trial that was published in The New England Journal of Medicine
in late 2016 and was presented at EMSO in the fall of 2016. It was a randomized trial of 500 women with high-grade ovarian cancer who had recurrent cancer and were in receipt of platinum-based chemotherapy. Eligibility included many different things, but mainly, they had to be sensitive—meaning the cancer needed to be sensitive to the current platinum based chemotherapy, which would mean the patient was having a reduction in her CA125 and tumor burden. Often though, these patients had to have cancer that was sensitive to the previous platinum, called the penultimate platinum—so it was the second-to-last platinum. There is a theme here—all of these patients had to have platinum-sensitive cancers.
They were then randomized 2:1 to either niraparib or placebo and underwent germline BRCA
tests, then put into 2 groups—germline BRCA
positive or germline BRCA
negative. Then the germline BRCA
negative group underwent retrospective homologous recombination deficiency (HRD) testing on the cancer. And this was shown in all of these different groups—germline BRCA
, non-germline BRCA
, and HRD negative—all of the groups showed a benefit of receiving niraparib as compared to placebo.
Simply put, when the patients finished chemotherapy, they were then randomized to niraparib or placebo. Niraparib was not added to chemotherapy, but was used more as a maintenance therapy, much like tamoxifen is used after initial breast cancer treatment.Niraparib was approved with a broad label, not requiring a BRCA mutation. Do you think that signifies that it will be widely used?
I do think that niraparib is going to be widely used because of the broad label. But, why is that significant? Because it broadens the applicability of a PARP inhibitor to non-BRCA
cancers, allowing more women to be candidates for this trial—it broadens the patient population, as well. It also gives patients more choices about their treatment.
This is exciting because ovarian cancer is unlike other cancers, where you read about FDA approvals nearly every week. This is really only the third drug that has been approved for ovarian cancer since 2006. That’s 3 drugs in 11 years.What lead to the priority review of olaparib in the maintenance setting?