Molecular Testing Continues to Evolve in Ovarian Cancer

Jubilee Brown, MD

As PARP inhibitors have showcased a survival benefit in select patients with ovarian cancer, Jubilee Brown, MD, explains that there must be a widespread approach to conduct molecular testing in all patients with the disease to provide them with a personalized treatment approach.

“Every single patient with ovarian cancer should be tested for germline and somatic mutations at diagnosis without exception,” said Brown, a professor of gynecologic oncology at Levine Cancer Institute, Atrium Health.

An example of promising data with PARP inhibition was the SOLO-1 trial, in which there was a 70% reduction in the risk of disease progression or death with olaparib (Lynparza) compared with placebo in patients with BRCA-mutant ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001).

Moreover, Brown recommends that physicians look for germline and somatic mutations when testing patients and their family members as a method to not only create a personalized treatment plan for patients with ovarian cancer, but also to prevent disease in those who may also harbor inherited genes.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer and Sarcoma, Brown discussed the importance of molecular testing immediately after an ovarian cancer diagnosis and how molecular testing will shape the field of ovarian cancer.

OncLive: Could you explain the significance of molecular testing for patients with ovarian cancer?

Brown: So much has changed in the field in the last several years. We have the capacity now to test patients with ovarian cancer for both germline and somatic mutations. When we combine this information, it radically changes how we can treat patients. With the addition of the SOLO-1 trial, now we know that patients who have both germline or somatic mutations in BRCA can really benefit from treatment with a PARP inhibitor; there's a 70% reduction in the risk of recurrence in these patients with ovarian cancer. It's really incumbent upon us to recommend treatment for our patients with either germline or somatic BRCA-mutant ovarian cancer.

What factors are you taking into consideration when you're conducting molecular testing?

Now, based on these data, all patients with ovarian cancer need to have molecular profiling. Upfront, 7% of patients will have BRCA-related mutations—that impacts how we treat these patients. They should all have maintenance therapy with a PARP inhibitor.

Additionally, even the National Comprehensive Cancer Network guidelines now tell us that patients with recurrent disease should be tested with molecular profiling to evaluate for somatic mutations. This often impacts what we can offer our patients, whether it's a clinical trial that gives them options for treatment that they wouldn't otherwise have, or an off-protocol option—commercially available agents, such as immunotherapy—that may be useful for these patients.

Could you expand on the benefits of germline testing?

When we talk about germline testing, we're talking about [the search] for inherited mutations. Those can be things like BRCA1 or BRCA2 mutations. There are also other less common germline mutations that confer risk for other cancers; therefore, surveillance for those cancers is really important. Additionally, testing the family members of patients with inherited mutations is important because we can prevent cancers in those patients completely.

On the other hand, when we discuss somatic mutations, we're looking for mutations that arise within the tumor itself. Those things aren't necessarily as common as germline mutations. They are a wider range of mutations. Even with rare ovarian cancers, we can find targets. These are called actionable mutations, meaning we can actually target the tumor with drugs that are more likely to work. This is cutting-edge science and we're gathering lots of information. Hopefully, in the next few years we'll be able to target these specific tumor types with very specific drugs that will work.

How do you see the role of molecular testing evolving in the future?

It's a huge, wide-open field. Over the next several years, we're going to be able to refine who gets treated with what drug based on very smart technology and molecular profiling. We'll be able to decide which drug is best for which patient—not just based on how something looks under the microscope, but based on personalized medicine.

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.