Ursula A. Matulonis, MD, discusses results of the phase III NOVA trial showed the PARP inhibitor niraparib demonstrated an improvement in PFS versus placebo as a maintenance therapy for patients with high-grade serous ovarian cancer.
Ursula A. Matulonis, MD
Results of the phase III NOVA trial showed the PARP inhibitor niraparib demonstrated an improvement in PFS versus placebo as a maintenance therapy for patients with high-grade serous ovarian cancer.
In an interview withTargeted Oncology, NOVA study author Ursula A. Matulonis, MD, professor of Medicine, Harvard Medical School, medical director of Gynecologic Oncology, Dana-Farber Cancer Institute, discussed the findings of the study, as well as other exciting maintenance therapy advancements in the field of ovarian cancer.
TARGETED ONCOLOGY:You are presenting a phase III study that evaluated niraparib maintenance therapy for patients with high-grade serous ovarian cancer. Can you give an overview of this trial?
This is a trial that started a number of years ago. It’s called the NOVA trial and it’s examining the PARP inhibitor niraparib. Niraparib is an oral PARP inhibitor, and it’s very potent. The trial design is that women had to have platinum-sensitive, recurrent ovarian cancer. They also had to have a special type of histology called a high-grade serous ovarian cancer.
The groups were broken into whether or not they had a germlineBRCAmutation or if their cancer responded positive to the homologous recombination deficiency (HRD) test. It’s basically a test that would indicate that the cancer possibly would be more sensitive to a PARP inhibitor if the test were positive versus negative, really taking out the germlineBRCAthat is a major driver of PARP inhibitor sensitivity.
It was a 2:1 randomization, and several hundred patients were enrolled. The data has now been published in theNew England Journal of Medicine.It was published late 2016 showing an improvement for progression-free survival (PFS) for women who receive niraparib versus placebo. They finished up chemotherapy and then they were randomized to either niraparib versus placebo.
I think the really good part of this, and the not unanticipated part as well, is that all groups of women entered onto the trial. If you looked at the patient population in different ways does she have a germlineBRCAmutation, does she have an HRD-positive tumor, or not. All of those groups derived benefit from receiving the PARP inhibitor niraparib after chemotherapy was completed versus placebo.
TARGETED ONCOLOGY:Are there any next steps planned for this study?
Niraparib is currently being reviewed by the FDA and the date for a decision is in June. Obviously, everyone is hoping that it will be earlier than June, but I think that is the published date for the FDA’s decision.
TARGETED ONCOLOGY:Are there any other advancements being made with maintenance therapy that you are excited about?
Ovarian cancer as a whole is not just 1 cancer. The reason that we certainly have made strides, especially with PARP inhibitor activity, and now PARP inhibitor approvals, is really by identifying different subgroups of ovarian cancer patients, such as high-grade serous ovarian cancer, which is very sensitive to platinum-based chemotherapy and very sensitive to PARP inhibitors.
Other types are clear cell cancer, mucinous tumors, endometroids, and low-grade serous cancers. I think another true maintenance therapy, where you use the therapy after platinum-based chemotherapy, is in patients with low-grade serous cancers. There was a presentation at ASCO in 2016, and the publication just came out from the MD Anderson group, looking at aromatase inhibitors as maintenance therapy post-platinum based chemotherapy for patients with low-grade serous cancers. It showed the women who received the aromatase inhibitor had an improvement in PFS, compared to not receiving. It really showed that tumor is a hormonally-driven cancer, whereas high-grade serous cancers are really driven by defects in DNA repair.
TARGETED ONCOLOGY:PARP inhibitors are being used in ovarian and breast cancer. Are they being looked at in any other types of cancers?
Absolutely. The oncology community are finding underlyingBRCA1 and 2 mutations in other cancers besides breast and ovarian cancer, specifically prostate cancer. There was a greatNew England Journalarticle recently showing there are mutations and PARP inhibitors are going to have activity. The same is true with pancreas cancer. I think a lot of cancers are now being found to have underlying defects in DNA repair, so we are really broadening the patient population to see who is going to benefit from a PARP inhibitor beyond breast cancer.