Novel Maintenance Combination in Advanced Ovarian Cancer - Episode 4

What's Next in Advanced Ovarian Cancer?

Bradley J. Monk, MD, FACOG, FACS:The treatment of newly diagnosed advanced ovarian cancer has changed and is changing. It changed by adding neoadjuvant chemotherapy. About half of patients now begin with chemotherapy rather than surgery. The surgery now is interdigitated between the third and the fourth dose. That makes the surgery easier. It does not compromise survival, again, but only in patients who have widely metastatic disease. That is change No. 1.

Change No. 2 is that we can add bevacizumab to the chemotherapy, and in the maintenance phase, as per the June 2018 FDA approval, and again, improve progression-free survival. And then in December 2018, we found that we could add olaparib in the maintenance phase if you had aBRCAmutation. Now the new study demonstrates that if you have an HRD [homologous recombination deficiency] signature beyondBRCA, you can either use a PARP inhibitor alone—niraparib or veliparib—or the combination of bevacizumab and olaparib. So the treatment has changed—neoadjuvant chemotherapy and bevacizumab—and is changing now beyondBRCAin combinations of olaparib with bevacizumab. The point is, patients are living longer. They’re living better, and that’s why we do this—to improve clinical outcomes to help patients live longer and better.

One of the recent discoveries has been that HRD, or homologous recombination deficiency, is not only a predictive biomarker of PARP sensitivity and chemotherapy sensitivity—meaning if the patient is HRD-positive, chemotherapy is going to work and a PARP inhibitor is going to work—but also has prognostic significance. If you are not HRD-positive, the patient is going to do poorly no matter what you do. Chemotherapy and a PARP is not going to work. In fact, in a high-risk subset, the median time to progression is between 5 and 6 months. Those are the patients who develop platinum-resistant recurrent disease, and that’s the unmet need.

Our hope is that we can add bevacizumab and atezolizumab together—that we can do a VEGF inhibitor and I/O [immuno-oncology] combination, which is a paradigm that has been validated in multiple other tumor types. That phase III trial of frontline bevacizumab plus atezolizumab has completed enrollment, and we’ll report in 2020. Or rather than PARP/anti-VEGF, do PARP and I/O.

There are also a number of trials with the checkpoint inhibitors that you know of—nivolumab, pembrolizumab, dostarlimab, and durvalumab. Those trials are enrolling, and really that’s what I would hope that you would do: Enroll your patients on those studies that are PARP with I/O. There are 4 of them. They’re really everywhere, and that’s certainly my standard of care: A clinical trial with 1 of these studies. But I think that’s the point. Patients need maintenance. HRD-positive patients need bevacizumab, and HRD-negative patients need a clinical trial.

Transcript edited for clarity.