Active Clinical Trials of Interest in Endometrial Cancer Explore Novel Up-Front Approaches

Bradley R. Corr, MD

Comparing the use of novel immunotherapeutic approaches with standard chemotherapy in the frontline setting represents a key focus of research in the endometrial cancer paradigm, according to Bradley R. Corr, MD.

“Some of the most exciting trials that are coming out are going to look [at how to best leverage immunotherapy agents as] up-front therapy,” Corr said. “One of the questions that [we hope to] answer in the not-to-distant future is: Is immunotherapy better, equivalent, or worse than chemotherapy? Combination therapy or single-agent [treatment] with immunotherapy could end up replacing chemotherapy.”

The phase 3 LEAP-001 (NCT03884101) and GOG-3064 (NCT05173987) trials are comparing the use of immunotherapy approaches with chemotherapy in those with endometrial cancer. Specifically, LEAP-001 is comparing the efficacy of frontline pembrolizumab (Keytruda) plus lenvatinib (Lenvima) vs chemotherapy in patients with stage III, IV, or recurrent disease, and GOG-3064 is evaluating the safety and efficacy of pembrolizumab vs carboplatin/paclitaxel in patients with mismatch repair deficient (dMMR) advanced or recurrent disease who did not previously receive systemic chemotherapy.

In an interview with OncLive^® during the 2022 SGO Winter Meeting, Corr, an assistant professor of the gynecologic oncology team in the Division of Gynecologic Oncology at University of Colorado (UC) Anschutz Medical Campus, of UCHealth, discussed practice-changing developments and active clinical trials that are being done in endometrial cancer.

OncLive^®: What are some of the key areas that active clinical trials are focused on exploring further in the realm of endometrial cancer?

Corr: [Several] active clinical trials are [being done] in endometrial cancer, [and they really give us] a sense of where treatment is [headed]. In [this disease], a big focus is onimmunotherapy, and specifically checkpoint blockade. Several clinical trials are evaluatingimmunotherapy in either combination with chemotherapy or as single-agent therapy.

Could you expand on the factors that should be considered when determining whether immunotherapy, chemotherapy, or a combination should be leveraged?

Right now, we see a lot of biomarker-driven therapies, [and with these, we are] thinking about mismatch repair deficiency or microsatellite instability [MSI]. These markers [can potentially dictate] whether combination strategies or single-agent immunotherapy checkpoint blockade will be effective or not.

Adding in the instrumental aspect of combining [immunotherapy] with standard chemotherapies like carboplatin and paclitaxel is where a lot of the questions [exist, and we hope they] are going to be answered. Alongside that, [we want to see whether] any of the combination therapies or single-agent therapies that we already have approved [for use] in recurrent cancers, [and be moved] into up-front therapy.

What ongoing trials are you most excited about?

Right now, the landscape of endometrial cancer trials is quite robust; it is an exciting time [for research]. Some of the trials that I am most interested in are [examining] up-front [approaches]—specifically immunotherapy vs chemotherapy, rather than combination. The [phase 3] LEAP-001 trial and the [phase 3] GOG-3064 trial are [both] evaluating [immunotherapy vs chemotherapy] in those with this disease.

I'm also interested in [the work that is being done with] small molecule inhibitors, some of the single-agent targeted therapies [that are under investigation] in the recurrent setting in various endometrial cancers. [Data on these approaches are anticipated,] far as efficacy and tolerability [goes].

What would you say is the most significant recent advancement that has been made in this disease?

As far as FDA-approved advances, the combination of pembrolizumab and lenvatinib has been game changing; it is standard of care for recurrent microsatellite stable tumors. Where I see all the shifting is how much to incorporate chemotherapy in up-front therapy [and whether we should incorporate chemotherapy at all]. That's where [research is being] focused.

How will molecular profiling help inform clinician decisions?

Molecular profiling is quickly becoming a standard of care for all endometrial cancers because it is dictating appropriate therapies. This field is advancing significantly. Currently, the National Comprehensive Cancer Network guidelines has recommendations for standard mismatch repair, as well as POLE and p53 mutations.

As this develops, we are finding new molecular markers, and we are finding efficacious therapies [targeting these] molecular markers. It is helping not only dictate which therapies work, but also which tumors do not need [treatment]. That is helping our clinical trial development, as well as what therapies to offer our patients.