Dr Bradley Monk on the Changing Regulatory Landscape of PARP Inhibitors

December 26, 2020
Rose McNulty

Bradley Monk, MD, FACOG, FACS, a professor at the University of Arizona, chronicles the regulatory changes in PARP inhibitors as they gain more indications in ovarian cancer.

Bradley Monk, MD, FACOG, FACS, a professor at the University of Arizona and Creighton University in Phoenix and clinician at Arizona Oncology, chronicles the regulatory changes in PARP inhibitors as they gain more indications in ovarian cancer.

Transcript

What have been some key developments in the regulatory landscape of PARP inhibitors since they were first approved in ovarian cancer in 2014?

The most recent advancement in PARP inhibitors has been the use of PARP inhibitors in frontline, newly diagnosed advanced ovarian cancer. The first really amazing study was SOLO1, published in the New England Journal of Medicine. The first author, of course, is Kathleen Moore. And that showed in maintenance frontline—again, now in the molecularly defined population of BRCA only—had a dramatic improvement in progression-free survival. And we're hoping that someday, frontline, PARP inhibition in newly diagnosed advanced ovarian cancer in BRCA patients will improve overall survival.

SOLO1 was a practice-changing, licensing enabling, reimbursement sort of definitive trial, but only in patients with BRCA-mutated, newly diagnosed advanced ovarian cancer that responded to chemotherapy. The challenge, though, was it was in a very well-defined but small patient population, those that had somatic or germline BRCA mutations. So somatic mutations, tumor tests, maybe 5%-10%; in germline, maybe 15%-20%. So it was only about a quarter of the patients. So then what happened is we launched this international collaboration to go beyond BRCA-mutated patients. And there is a molecular signature that I've sort of alluded to, homologous recombination repair deficiency [HRD], which can be ordered either through Foundation Medicine or through Myriad, which identifies BRCA-like genes where there might be a broader opportunity for PARP inhibition.

We launched that study collaborating with the GOG in the European Network, and we showed that we could utilize PARP inhibitors beyond BRCA, this time niraparib in a study called PRIMA published in the New England Journal of Medicine in December of 2019. [It was] FDA approved on April 29, 2020, beyond BRCA.In fact, it works so well that the FDA said not only can you use it in BRCA, but BRCA-like genes, and HRD. You can use it in all comers. And the study personalized the dose, and niraparib is the only once-daily PARP inhibitor, so a very distinguishing quality. Beyond BRCA, all comers, once daily, and a personalized dose.