New Therapies Offer More Precision Treatment for Ovarian Cancer

John Diaz, MD

The ovarian cancer treatment landscape has exploded with precision oncology options that offer oncologists the opportunity to achieve better outcomes for their patients without added toxicity, according to John Diaz, MD.¹

At the Inaugural Miami Cancer Institute Precision Medicine Oncology Symposium, Diaz, the chief of Gynecologic Oncology, lead physician for Clinical Trials in Gynecologic Oncology at MCI, and chief of the Center of Excellence in Minimally Invasive Gynecologic Surgery, Baptist Health South Florida, gave a presentation on the role of precision medicine in the management of ovarian cancer.

“The goal of my presentation is sharing this evolving field with my peers, particularly those who may not have as much experience in the treatment of ovarian cancer through targeted therapies. It's so important that we maintain an excellent standard of treatment for these women and understand those tools that are available to us. We have to understand how to interpret these reports, and how to ensure that we have the best outcomes for our patients utilizing the latest technology and novel treatments,” Diaz told Targeted Oncology™, in an interview.

According to Diaz, PARP inhibitors have had the most success in ovarian cancer treatment. However, through genomic testing, oncologists can also determine which patients are eligible for immunotherapies, therapies that target folate receptor α and antibody-drug conjugates.

In an interview, Diaz summarized the ovarian cancer treatment, and discussed the role of genomic testing and novel targets.

TARGETED ONCOLOGY: Can you give an overview of your presentation?

Diaz: At the symposium, I discussed the role of precision medicine in the management of ovarian cancer. This is an area that has evolved quickly over the last several years. Precision medicine has helped us to tailor the treatment of ovarian cancer based on genetic markers to improve patient outcomes and minimize unnecessary toxicities.

Can you discuss the targeted therapies that are showing promise in the ovarian cancer space?

A class of drugs that gained a lot of attention in ovarian cancer over the last 10 years are PARP inhibitors. PARP inhibitors are an oral medication that patients with ovarian cancer can take after completing their platinum-based chemotherapy. PARP inhibitors have moved up now to first-line maintenance therapy. Selecting the appropriate patient for a PARP inhibitor is based on genomic testing.

All women with a newly diagnosed ovarian cancer are referred to our geneticists and undergo germline testing to look and see if they have a hereditary mutation, such as BRCA1 and BRCA2. In addition, the patient's tumor is evaluated to see if they have any indicators, or genomic markers, that would then determine they would have a positive response to maintenance therapy with 1 of the PARP inhibitors. Depending on the patient’s germline mutations, or tumor genomic markers, we then tailor these patients’ maintenance therapy to a PARP inhibitor, and now, potentially a PARP inhibitor in combination with a VEGF inhibitor such as bevacizumab [Avastin]. Randomized trials have shown that women who have tailored therapy with PARP inhibition or PARP inhibition combined with VEGF inhibition have better outcomes than those patients who don't have these biomarkers or receive no further maintenance therapy.

What are the key challenges with utilizing targeted therapies in this space?

As gynecologic oncologists, we're a little bit behind our colleagues in medical oncology who have had the opportunity to utilize precision medicine in the treatment of lung cancer and melanoma. We've been a little bit slow to uptake, but over the last few years, there have been a lot of advancements in identifying those women with ovarian cancer who would benefit from precision medicine.

In recent years, we've seen an indication whereby you can look at these individual patients’ genomic markers and determine who has the best benefit of a PARP inhibitor per se, as well as a potential benefit for immunotherapy. This has helped us to improve our patient outcomes with tailored delivery medications. Most recently, the FDA approved the new medication for patients with ovarian can who have the biomarker for folate receptor. This has been a huge accomplishment in the treatment of platinum-resistant ovarian cancer, where we have limited effective tools. This has been a big breakthrough for those of us in gynecologic oncology to utilize precision medicine for the treatment of our patients.

What are some innovations you see coming in the ovarian cancer space in the future?

Ovarian cancer is an umbrella term and under that are cancers that begin in the ovary, cancers that begin in the fallopian tubes, or peritoneal cancers. Ovarian cancers represent a heterogeneous group of patients and we've known this since the 1930s. The challenge has been we've never had a great way to determine these different cancers, their genomes and how best to treat them, so we kind of took a one-size-fits-all approach.

Our patients are treated with a combination, usually of carboplatin and paclitaxel, and while we had good results with that, the advent of precision medicine allows us to identify specific markers for these patients, so that we can target specific pathways that each individual patient will respond best to.

As we move forward, we're identifying additional targets in ovarian cancer. We're also using a combination of treatments. We’re looking at various targets and combinations to attack and fight this cancer and different pathways.

What are some known biomarkers in ovarian cancer that you would like to see more research on in the future?

One of the exciting advances that we've seen in gynecologic cancers is the utilization of antibody-drug conjugates. When I talk to my patients about these drugs, I use the analogy of thinking of them as a Trojan horse. They have now been utilized for both ovarian cancer and cervical cancer, and we have 2 FDA-approved antibody-drug conjugates for the treatment of gynecologic malignancies. One of the targets are these folate receptor agonists, and there are several more in the pipeline.

It's exciting to see that we have these targeted therapies. We're going to start to have to understand how we use these treatments in patients who have already been exposed to folate receptors. Then, we have to identify additional receptors that we can utilize for these targeted treatments.

What should oncologist takeaway from your presentation?

The goal of my presentation is sharing this evolving field with my peers, particularly those who may not have as much experience in the treatment of ovarian cancer through targeted therapies. It's important that we maintain an excellent standard of treatment for these women and understand those tools that are available to us. We have to understand how to interpret these reports, and ensure that we have the best outcomes for our patients utilizing the latest technologies and novel treatments.

_REFERENCE:

_{1 Diaz J. Role of Precision Medicine in the Management of Ovarian Cancer. Presented at Inaugural Miami Cancer Institute Precision Oncology Symposium; February 3-4, 2022; Coral Gables, FL}