Real-World Analysis Informs Future Directions for Evaluating Dostarlimab/Chemotherapy in Advanced Endometrial Cancer

Taliya Lantsman, MD

Following the readout out of practice-changing data from the phase 3 RUBY (NCT03981796) and NRG GY018 (NCT03914612) trials, a retrospective analysis has shown that progression-free survival (PFS) outcomes with dostarlimab-gxly (Jemperli) plus chemotherapy among patients with advanced or recurrent endometrial cancer from RUBY were comparable to those treated in a real-world setting, according to Taliya Lantsman, MD.

At the first interim analysis of RUBY, with a data cutoff of September 28, 2022, dostarlimab plus carboplatin/paclitaxel demonstrated statistically significant improvements in both the mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H; HR, 0.29; 95% CI, 0.16-0.50; P < .0001) and overall patient populations (HR, 0.64; 95% CI, 0.51-0.80; P < .0001). 1

The NRG GY018 study evaluated pembrolizumab (Keytruda) plus carboplatin/paclitaxel in advanced, metastatic, or recurrent endometrial cancer.2 Notably, the HRs indicated a favorable PFS per blinded independent central review with pembrolizumab vs placebo in the mismatch repair–proficient (pMMR; HR, 0.64; 95% CI, 0.49-0.85; P = .0008) and dMMR (HR, 0.45; 95% CI, 0.27-0.73; P = .0005) groups.

“[These trials led to] a significant change [in practice] from what was previously done in the advanced endometrial cancer space,” Lantsman said in an interview with OncLive®. “However, with any clinical trial, there is always a consideration of who was being evaluated and how we can apply this study to our own patients [in the real-world setting].”

During the interview, Lantsman highlighted the rationale for evaluating dostarlimab plus chemotherapy in advanced endometrial cancer, real-world efficacy findings with the combination, and the clinical implications of these data.

Lantsman is a hematology/oncology fellow at the Beth Israel Deaconess Medical Center in Boston, Massachusetts.

OncLive: What was the background and rationale for this real-world analysis?

Lantsman: In 2023, [data from] RUBY and NRG GY018 trials came out, and they looked at adding immune checkpoint inhibitors to platinum doublets in endometrial cancer. [In our analysis,] we wanted to look at patients in our clinic and see whether they were receiving the same benefits and had similar rates of adverse effects [AEs], as [what was] seen in the RUBY trial.

What patient population was included?

We did a retrospective analysis on patients at our single academic institution. Altogether, we had 27 patients doing a chart review. We evaluated their baseline characteristics, the types of treatments they received, AEs they experienced when they had disease progression, why they progressed, the treatments they received afterward, and where they are now.

How did the real-world efficacy with this combination compare with that seen in clinical trials?

We had a small patient population of 27 patients. Six of them had stage III endometrial cancer, and the rest of them had stage IV or had recurrent endometrial cancer. We saw a wide range of histologies evaluated. Focusing on stage III disease, at our institution, we gave radiation to these patients, which differs from what we saw in RUBY, where radiation was not given. Interestingly, none of these patients, at the time of analysis, had disease progression or recurrence. Looking at our stage IV patients, a majority of them had higher-risk histologies, and then when you look at AEs, we saw similar ones as noted on RUBY. We also saw that patients tolerated immune checkpoint inhibitors well. Only 9% of patients had to discontinue treatment due to an AE. We evaluated the patients who did experience disease progression; that's where we're interested in this space. Some patients received pembrolizumab plus lenvatinib [Lenvima], some went on to receive an antibody-drug conjugate, some went on clinical trials, and others had other treatments. Overall, out of 27 patients at the time of analysis, 2 patients had died of their disease.

What are the implications of these data for clinical practice and future research directions?

All in all, this analysis demonstrates that we can use dostarlimab in addition to platinum doublets in the advanced endometrial cancer space, but we still have many questions in that space as well. Are certain people doing better with the addition of dostarlimab? Of course, we expect that patients with pMMR disease may not do as well as patients with dMMR disease, but even one step further, based on next-generation sequencing, that's an interesting question to ask. Another consideration is that our patients received radiation. The radiation question wasn't discussed in RUBY, and it is an interesting [aspect to consider]. Further, what's reassuring is that our patients who received radiation didn't have any increased AEs based on being on immunotherapy and radiation simultaneously. Lastly is the question of what to do next. Are we okay with using an immune checkpoint inhibitor after progression on immune checkpoint inhibitors? Does sequencing matter at all? These are the essential questions that we need to ask in the future.

Are there any specific planned or ongoing analyses based on this real-world analysis?

We're still collecting data to get more patients and have further follow-up. At this time, we have [approximately] 214 days of follow-up, but since this is a newer combination, we're slowly adding people onto [the study]. I hope we get more data from it soon.

References

1. Lantsman T, Jia L, Edmiston C, Shea M, Widick P. Real-world RUBY: safety and efficacy of combination chemotherapy plus dostarlimab in advanced endometrial cancer. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 1280.
2. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023;388(23):2145-2158. doi:10.1056/NEJMoa2216334
3. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial. Nat Med. 2025;31(5):1539-1546. doi:10.1038/s41591-025-03566-1