Dr Lantsman on Future Directions for Evaluating Dostarlimab/Chemo in Endometrial Cancer

“All in all, this [retrospective analysis] demonstrates that we can use dostarlimab in addition to platinum doublets in the advanced endometrial cancer space, but we still have a lot of questions [that need to be addressed] as well.”

Taliya Lantsman, MD, a hematology/oncology fellow at Beth Israel Deaconess Medical Center, highlighted future research directions evaluating the treatment of dostarlimab-gxly (Jemperli) plus chemotherapy in real-world patients with advanced endometrial cancer.

In a real-world, retrospective, single-institution analysis, 27 patients with stage III/IV or recurrent endometrial cancer were included, and data showed they experienced progression-free survival (PFS) outcomes comparable to data from the phase 3 RUBY trial (NCT03981796).

These real-world data further highlight the applicability of dostarlimab plus platinum doublets in the advanced endometrial cancer space, Lantsman began. In August 2024, the FDA approved dostarlimab in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This expanded on the combination’s original approval in July 2023, when it was indicated only for patients with mismatch repair deficient (dMMR)/microsatellite instability high disease.

However, Lantsman noted that there are remaining questions regarding the use of the combination in the real-world setting, including whether certain patients do better when dostarlimab is added to the regimen. Future research with next-generation sequencing may help parse out this question, especially as patients with mismatch repair–proficient endometrial cancer may not demonstrate greater benefits compared with those with dMMR disease, she explained.

Furthermore, patients in the real-world analysis had previously received radiation, which was not part of the RUBY trial, Lantsman said. She emphasized that this could be an opportunity for future directions. Notably, patients included in the analysis who were treated with radiation and immunotherapy simultaneously did not show an increased incidence of adverse effects (AEs), she continued. Other questions that warrant further research include the next steps of research, whether utilizing immune checkpoint inhibitors after disease progression is still feasible, and whether sequencing is important, Lantsman added.

In the analysis, those with stage IV disease with high-risk histologic subtypes were more frequently observed. Of note, the AE profile was also consistent with the safety data revealed from the RUBY trial. Nine percent of patients discontinued treatment because of AEs. Seven patients experienced disease progression, in which their post-progression treatments comprised pembrolizumab (Keytruda), antibody-drug conjugates, clinical trials, and other therapies.