Modesitt Spotlights the Latest ADC Breakthroughs in Gynecologic Oncology

Susan C. Modesitt, MD, FACOG, FACS

In an interview with OncLive^®, Susan C. Modesitt, MD, FACOG, FACS, sheds light on the latest advancements and research with antibody-drug conjugates (ADCs) in gynecologic oncology, as discussed in her presentation at a recent OncLive State of the Science Summit™ on gynecologic oncology. This included insights on up-and-coming TROP2- and HER2-targeted ADCs and their evolving roles in clinical practice; the management of toxicities associated with ADC use; and the importance of staying abreast of evolving paradigms and clinical trials in gynecologic oncology to optimize patient outcomes and minimize toxicities.

“It’s a great time to be a gynecologic oncologist because we are now getting all these new agents that we’ve never had before,” Modesitt stated during the interview. “This is especially true for diseases that we didn’t think would respond to traditional chemotherapies, particularly recurrent endometrial cancer and recurrent cervical cancer.”

As chair of the event, Modesitt further discussed key takeaways from her colleagues’ presentations in a concurrent interview. Modesitt leads the gynecologic oncology program at Winship Cancer Institute of Emory University. She is also director of and a professor in the Division of Gynecologic Oncology at Emory University School of Medicine in Atlanta, Georgia.

OncLive: What updates are notable in ADC development within gynecologic oncology?

Modesitt: It was fun to start talking about some of the ADCs we have in current practice that most of us are getting a little bit more familiar with, and then starting to get a sneak peek at what the future may look like. We can tweak parts of ADCs and a lot of [questions regarding] some of these new ADCs that are going into trials [include]: Can we make it more specific to only go into tumor cells? Can we give the agent an alternative way of attacking the same tumor cell in case it doesn’t [express] the target? Can we reduce the bystander effect?

Things are changing every day in terms of what is available, what is now in the National Comprehensive Cancer Network guidelines, and what received fast track designation from the FDA. It’s exciting to go to meetings like this, as well as our upcoming national meetings, to figure out what’s new in the pipeline that we can employ for our patients.

What are the most promising ADCs coming down the pike in this space?

As we go through clinical trials, we always start with patients that have recurrent disease to see if [an agent] works and if there’s a signal—then we try and figure out where we should best use it. For example, should we be using mirvetuximab soravtansine-gynx [Elahere] more upfront or in the platinum-sensitive [ovarian cancer] setting, and not just for patients with platinum-resistant disease? Some of the current trials are looking [to answer] that [question].

The new kids on the block are TROP2-targeted agents and 1 of the promising ADCs that we have coming out is sacituzumab govitecan-hziy [Trodelvy], which is targeting TROP2 and has a topoisomerase attached to it; that is just coming through for many of us [treating patients with] recurrent endometrial cancer. One of the other ADCs that started in breast cancer is the HER2-targeted [agent] trastuzumab deruxtecan [Enhertu; T-DXd]. [This ADC] showed amazing results in the [phase 2] DESTINY-PanTumor02 [NCT04482309] trial and it has even been incorporated into the NCCN guidelines. Those are 2 ADCs to watch.

Some of the other agents that we are using include tisotumab vedotin-tftv [Tivdak] in cervical cancer [which we are giving] in the second and third line, but should we be using it at a different time? The jury’s still out. [Overall], there’s a lot of amazing [data] coming out, which all of us are excited about.

What treatment-related toxicities should clinicians be looking out for when using these ADCs, and how has the management of these toxicities improved with increased familiarity?

We’re still sorting it out. For those of us in gynecologic oncology, for example, we hadn’t used trastuzumab [Herceptin], but now we’re starting to use both the antibody form and the ADC form more for patients with HER2-positive disease, particularly in endometrial cancer. Thinking about [drug-associated] cardiac toxicity, it’s usually reversible, but you must follow echocardiograms which is something we don’t normally do for most of the other drugs we use. That’s 1 toxicity we must be hyper-aware of.

Interstitial lung disease is another toxicity that we must watch out for, particularly with T-DXd. Everybody’s pretty in tune with eye toxicities [associated with] tisotumab vedotin and mirvetuximab soravtansine—all of us are getting more comfortable asking people about their eyes, having an ophthalmology partner, making sure we’re doing steroid drops and lubricating drops, and having people not wear contacts. We’re gaining some familiarity with all these drugs, and it’s nice to have some more agents in our toolbox.

What is your main message for colleagues based on our discussion?

A lot is going on and it’s a great time to have some of these [events] where you can assess and figure out what is going on elsewhere. It’s hard to keep up with everything, so being able to see talks like this puts things into context with some of the experts in the field who are doing the research. What you think you know today may be wrong in 6 months. [It is important to] have a little humility about that and recognize that what I’m telling a patient today may be very different than what I’m going to tell them [even] a year from now.

What ongoing research in gynecologic oncology is occurring at your institution?

Like most academic institutions, we have a ton of trials ongoing. We have multiple phase 1, first-in-human trials, and 1 trial looking at new TROP2-targeted ADCs that are just about to open. Then I have 1 trial that’s near and dear to my own heart which is my own [looking] at some new drugs and trying to prevent neuropathy. It’s not just about living longer, it’s also about living better, so it’s nice to have the opportunity to get better treatments and less toxicities for our patients.