Modesitt Reflects on the Art of Treatment Selection Amidst Expansion of Targeted and Immunotherapies in Gynecologic Oncology

Susan C. Modesitt, MD, FACOG, FACS

From optimizing PARP inhibitor use in ovarian cancer to exploring biomarkers for targeted therapy in endometrial cancer, the field of gynecologic oncology aims to enhance patient care through an expansion of tailored treatment approaches, according to Susan C. Modesitt, MD, FACOG, FACS, who emphasizes the importance of shared decision-making, consideration of individual patient characteristics, and ongoing research to help navigate resulting complexities in treatment sequencing.

“As we saw in some of these presentations, all of us can look at the same data and come to disparate opinions, [and the right course of action] also may be different depending on what patient is sitting in front of us,” Modesitt said in an interview with OncLive^® regarding a recent OncLive State of the Science Summit™ on gynecologic cancers, which she chaired. “It gets back to [the idea that there’s] still a bit of art in medicine.”

In the interview, Modesitt expanded on key topics across gynecologic oncology that were discussed by her colleagues at the event. This included remaining questions regarding the optimal use of PARP inhibitors in ovarian cancer, the importance of shared decision-making and ongoing research to refine treatment strategies, key biomarkers of interest in endometrial cancer, and updates in cervical cancer management.

Modesitt leads the gynecologic oncology program at Winship Cancer Institute of Emory University and serves as the director, and is also a professor, in the Division of Gynecologic Oncology at Emory University School of Medicine in Atlanta, Georgia.

OncLive: What role do PARP inhibitors have in the ovarian cancer treatment paradigm according to current data, and what questions need to be answered to elucidate this further?

Modesitt: The bottom line is that if a patient has a BRCA mutation, whether somatic or genetic, or a homologous recombination deficiency, there is no question that they need to be on a frontline PARP inhibitor. The harder [decision] is for folks that don’t have those markers. When should we be using the PARP inhibitors? Should we use them up front or wait? Some of the emerging data are showing decreased survival [when they’re used in] that later line and we’re still [getting] long-term data on safety, time to subsequent therapies, and responses to subsequent therapies. We’re going to continue to monitor this, and everybody [approaches PARP inhibitor use] differently.

In [these] debates, clinicians look at the same data and come up with different scenarios to talk about with their patients. We have to remember that this is shared decision-making and we don’t know everything as physicians, so we can present the data to the patient and give a recommendation or the pros and cons. [However], if I [have a patient] that I don’t think would benefit that much from a PARP inhibitor because she doesn’t have the markers, but she says "Gosh, I really want to do it," I am happy to [treat her with a PARP inhibitor]. If I have a patient who I think needs a PARP inhibitor, and they decide they don’t [want to be on one], that is their decision, and I will support them in it. You can’t always follow the algorithm exactly, but these were game-changing drugs that every one of us is [using to] help prevent recurrence for our patients.

What were your key takeaways from the ovarian cancer case study presented by Guilherme Cantuaria, MD, PhD, FACOG, FACS, of the University Gynecology Oncology, during the meeting?

It’s always interesting to hear what other people do. Many of us are in an academic setting so we didn’t embrace, for example, bevacizumab [Avastin] maintenance for every single patient because there was no overall survival [OS] advantage. A lot of us were using it only in certain cases, whereas other folks use it for everybody just because [they are] not sure who it’s going to help and who it’s not. When the phase 3 PAOLA-1 trial [NCT02477644] data came out with bevacizumab plus a PARP inhibitor [it made some people] more likely to do both agents vs just 1.

We had people represented from multiple different institutions at the meeting and there was not necessarily a consensus on what the right thing is to do. Each patient is an individual and you may have to make different decisions based on what the patient has [previously received] during their course of treatment, what their disease status is, and all of that. It’s always good to have a multifaceted discussion.

What biomarkers are of interest for targeted therapy development in endometrial cancer? How do ongoing investigations of these therapies help further a more personalized approach to medicine?

Data was presented from the phase 3 NRG-GY018 [NCT03914612] and RUBY [NCT03981796] trials 1 year ago, and we were all tremendously excited [to see] patients with stage III/IV disease have appreciable improvements in both progression-free survival and OS. That is key. There’s a group of patients who may not respond as well which is similar to the PARP inhibitor groups [where] you have 3 tiers of responses. For endometrial cancer, we also may have different responses. [Additionally,] not everybody was eligible for those trials. In the patients who weren’t eligible for the trial who have less disease and fewer poor outcomes, should we be using immunotherapy? Those are some of the outstanding questions that still are being addressed right now. Should everybody get immunotherapy or should patients with mismatch repair–proficient disease be getting something else?

There are some new drugs coming down the pike for the P53 wild-type group of patients, such as selinexor [Xpovio] in the phase 3 XPORT-EC-042 trial [NCT05611931] and a few others. It’s exciting that we have a lot more options to offer our patients that truly [generate] meaningful improvements in survival. [We are] still trying to figure out who should get what, in what circumstance, and for how long. That is going to take us another 5 or 10 years to sort out, but I still remember when we had nothing to offer these patients besides adjuvant radiation, so it’s a great time for our patients.

What are some of the key updates in cervical cancer as presented by your colleague Sarah Dilley, MD, MPH, FACOG, of Winship Cancer Institute?

We’ve had immunotherapy trials that have [not met their primary end point] in the advanced upfront setting, and now we have a positive trial, which is exciting. We’re trying to sort through which patients might benefit from adding immunotherapy maintenance to their upfront chemotherapy and radiation. Dr Dilley did a nice job at summarizing what we know, what we don’t know, and what the current FDA recommendations are. We must go back now and figure out if [patients] had stage III disease [according to] the old criteria where we weren’t using radiographic testing or not.

[Dr Dilley then outlined] what the next steps are going to be, going over some antibody-drug conjugates and what’s available in the recurrent setting. She also touched a lot on prevention, which is great because it is easier to prevent cancer than to [manage] it. We can’t forget that it would be better if more women didn’t get cervical cancer [rather] than having better treatments. [Another question is] for women who aren’t cured, what should we be doing in the recurrent setting based on some of the trial data?