Ritu Salani, MD, MBA: Before we open this up to the panel, Bhavana, do you mind sharing a little about NRG-GY018? It was presented earlier this year as well. Highlight some of the differences between RUBY and the GY018 study.

Bhavana Pothuri, MD: GY018 was presented by Dr Ramez Eskander at SGO [Society of Gynecologic Oncology Annual Meeting on Women’s Cancer]. This trial looked at the addition of pembrolizumab vs placebo to the standard chemotherapy backbone. Much like RUBY, [the investigators] found an astounding benefit in the dMMR [mismatch repair deficient] patients with a hazard ratio of 0.3, while the mismatch repair proficient [MMRp] subgroup had a hazard ratio of 0.54. The thing that’s different is this trial was designed to have 2 separate analytics groups that were powered to detect a difference in each group. The preliminary data presented showed a benefit in both subgroups. This is practice changing, and there was benefit irrespective of biomarker status.

The other thing I want to highlight is that a quarter of these patients were from diverse backgrounds. Kudos to everyone in terms of improving diverse patient accrual and making sure these new therapies that we’re studying are available to all our patients. In endometrial cancer [we have a] rising incidence due to the obesity epidemic and an increase in mortality, which is largely due to high-risk histological subtypes that are disproportionately overrepresented in Black patients. It’s important that we include all these patients.

The other difference was the duration of immunotherapy use. It was 3 years in RUBY and 2 years in GY018. There was also a difference in terms of the disease assessments. They were done more frequently: every 6 weeks in RUBY in the beginning vs every 9 weeks in GY018. You’ll see some of those differences as you’re looking at your data.

There were also differences in terms of the treatment interval from the last platinum treatment when it was used in the adjuvant setting between the 2 trials.

Ritu Salani, MD, MBA: RUBY allowed for carcinosarcoma. They capped it at 10%, which is a small difference and predominantly in the MMRp population. But it’s clear to say that for the dMMR population, this is a clear win. This instantly changed how we treat these patients. What do you guys think about the MMRp population? You heard that the statistics and analysis were positive in GY018, and the PFS [progression-free survival] was positive in RUBY, which was a subgroup analysis. What’s your takeaway on this side of the table?

Ursula A. Matulonis, MD: I agree with what everyone said. For mismatch repair deficient [patients], it’s a clear win. We need to make sure all our patients are getting their IHC [immunohistochemistry] testing done up front and that it doesn’t get missed. We do this all the time, so we have to work with our pathologists on that. For mismatch repair proficient [patients], it has a category 1 on NCCN [National Comprehensive Cancer Network] Guidelines. The progression-free survival is different. It definitely deserves a conversation with a patient. I wouldn’t say, “Don’t do it,” but I’d [address] it on a case-by-case basis and have a discussion with the patient, because in certain patients it’s appropriate. As we get more information about the molecular profiling for the patient, maybe their TMB [tumor mutational burden] is a little higher. Certain histologies may not be as sensitive to immunotherapy, and we’re going to learn more as time goes on about different subset analyses. But for right now, before we have that, I’m definitely discussing it with patients with mismatch repair–proficient tumors and then going over the risks and benefits.

Shannon N. Westin, MD, MPH, FACOG: One other thing I’d highlight is that for GY018, for the group that was mismatch repair proficient, the follow-up isn’t as long as the follow-up time we had in RUBY. It will be interesting to see if that difference comes down to earth a little. But I agree, I’m very loath not to do some type of maintenance in these patients. I’ve been talking to all my patients, regardless of their biomarker, about these data and giving them the opportunity to interpret it as best we can. The majority of them want to do something. When you look at the curves, even for the proficient group, they flatten. Yes, there’s a group that’s not going to benefit from the addition of the immune checkpoint inhibitor, but there’s a group that will. Because I can’t completely tease that group out based on mismatch repair deficiency or proficiency, I’m interested in trying that until I have something better.

Matthew A. Powell, MD: We mentioned high-risk histologies, that serous [adenocarcinoma] population that was called out in the forest plot in GY018 clearly stays on the supporting I/O [immuno-oncology] therapy. It was a shock to many of us to see that the hardest-to-treat population, the 1 most associated with our Black patients, looks like it’s benefiting. We’ll know more in the next half year as all the molecular data hopefully are reported and dissect this further. It’s very exciting.

Bhavana Pothuri, MD: You bring up a good point. In serous cancers we also have the opportunity to use trastuzumab, which is NCCN listed. Ursula and I had this conversation. I’m curious to see how you think about that, trastuzumab vs pembrolizumab.

Matthew A. Powell, MD: We’re looking to see how the results of GY018 and RUBY affect our ongoing trial. An ongoing trial, GY026, is looking at not only the addition of trastuzumab but also pertuzumab delivered in the subcutaneous fashion for patients with HER2 [human epidermal growth factor receptor 2]–positive endometrial cancers. They’re mostly serous but TP53 abnormal, and we’re adding carcinosarcomas. Do we choose I/O or a HER2-targeted [therapy]? We’re collecting data from GY018 to see how those patients did who are HER2+. It won’t be perfect, but it’s hypothesis generating. We need to modify GY026 to add a checkpoint.

Ritu Salani, MD, MBA: That’s great. It’s exciting to have multiple studies that will be informative. We also have selinexor, which is looking at maintenance and focusing on the TP53 wild type after platinum-based therapy, either in the frontline or recurrent settings. There’s more to come in this space.

Transcript edited for clarity.