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Thomas Herzog, MD, discusses recent changes in the ovarian cancer landscape, specifically PARP inhibitors and the optimal use of bevacizumab.
Thomas Herzog, MD
A key message from the phase III SOLO-1 trial is that patients with ovarian cancer should be tested for BRCA mutations quickly after diagnosis to inform physicians what treatment will be most effective, explained Thomas Herzog, MD.
Results of the study led to changes in practice and emphasized the importance of frontline therapy, according to Herzog. In the study, treatment with olaparib led to a 70% reduction in the risk of disease progression or death compared with placebo in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001).
Before SOLO-1, Herzog explained that physicians conducted BRCA-mutation testing to see if patients were eligible for platinum-based therapy in the maintenance, third-, or fourth-line treatment. However, data demonstrates BRCA status impacts frontline therapy decisions. Physicians should test patients for the BRCA mutation in order to create an individualized treatment from the start, according to Herzog.
“As we move forward, treatment is going to be more personalized medicine based on histology, molecular signature, and genomic sequencing. Using that, we will put together the best cocktail for the patient upfront and maybe eradicate all the cancer cells so we don't have the recurrence, because once we have the recurrence, the chances for cure are very minimal,” said Herzog, a professor of obstetrics and gynecology and deputy director at University of Cincinnati Cancer Institute.
In an interview during the 2019 OncLive® State of the Science Summit™ on Ovarian Cancer and Sarcoma, Herzog discussed recent changes in the ovarian cancer landscape, specifically PARP inhibitors and the optimal use of bevacizumab (Avastin).
OncLive: How has treatment for ovarian cancer progressed in recent years?
Herzog: We have not made not a lot of progress in ovarian cancer treatment in the last 20 years from the standpoint of changing standard of care for frontline disease. However, we have had tremendous impact in terms of looking at new approvals. Those approvals have largely been in maintenance for second-line therapies and beyond that. We also have had an approval for bevacizumab for frontline therapy. With PARP inhibitors and bevacizumab, there have been a lot of developments in the last few years that have made a big difference in the treatment of patients with ovarian cancer.
How have PARP inhibitors changed the ovarian cancer landscape?
In terms of looking at the two classes of agents that have had the greatest impact thus far, it's really been antiangiogenic inhibitors, such as bevacizumab, and PARP inhibitors. We have 3 PARP inhibitors that have been approved by the FDA: olaparib, rucaparib (Rubraca), and niraparib (Zejula). Each of these agents have been able to show progression-free survival improvement over time. It's important to understand that these agents, while they show PFS advantage, are only the beginning of our understanding of how these agents benefit the patients.
We have BRCA as a biomarker for PARP inhibitors. We also know that the biomarker extends into homologous combination deficiency. Yet, we see in platinum-sensitive disease with maintenance therapy, that there is a benefit even in patients who do not exhibit either of those characteristics. With bevacizumab, one of the big challenges is identifying the patients who will benefit the most. We have not been able to develop a biomarker successfully to date, but we still see that bevacizumab is helpful in platinum-resistant disease, platinum-sensitive disease, and frontline disease, all of which are approved.
What challenges still exist in ovarian cancer?
The biggest unmet need in ovarian cancer is a cure; that's where the greatest challenge exists. If we look at patients today who have presented to us normally, 75% of those patients will present at an advanced stage of disease. If you look at that group of patients and try to predict recurrence, we know almost 75% of them will recur. How do we keep that from happening? We need to intervene at the earliest parts of the disease process, which would be frontline treatment.
What considerations should a physician make when deciding treatment for patients with ovarian cancer?
The first question you need to ask is where the patient is positioned on the treatment timeline. For frontline disease, one of the things that has become very clear in the last year is we need to know the BRCA status of the patient. Previously, we would say it's not that important and that we'll use it as a signature later on to determine if the patient is a candidate for platinum-sensitive maintenance or platinum-based therapy in the third- or fourth-line setting. Right now, since we have SOLO-1 data showing the amazing results in frontline therapy, we need to know BRCA status much sooner. Testing as soon as possible is really important, both for germline and somatic BRCA mutations.
What are the main points that you want to convey about ovarian cancer treatment?
We've spent billions of dollars not making a lot of progress and just adding on to the chemotherapy backbone until we hit upon bevacizumab and PARP inhibitors. Those therapies have made a difference in terms of improved PFS and hopefully overall survival. Looking at the SOLO-1 results, we hope that we may even be able to cure more women with ovarian cancer, but that remains to be seen. It’s a very optimistic view, but one that I hope occurs.
What the key takeaway for ovarian cancer treatment?
Testing for BRCA at an early enough stage or point in the timeline is important to make a difference for an individual patient. If we don't know that upfront, we may miss that original opportunity for frontline maintenance, which could be the best chance for cure. We could miss even the chance for platinum-sensitive maintenance, which has shown a significant advantage in terms of PFS and really improve the patient's quality of life. The real message here is: we need to understand who to test—the earlier the better. We have changed the trajectory of ovarian cancer with understanding these biomarkers.
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505. doi: 10.1056/NEJMoa1810858