How would you sequence adjuvant chemo-immunotherapy (paclitaxel/carbo/pembro or paclitaxel/carbo/dostarlimab) with EBRT and vaginal cuff brachytherapy in advanced uterine cancer that meets clinical criteria for both EBRT and chemo-IO?

A common misapplication of RUBY/GY018 is giving IO in patients with non-measurable advanced uterine cancer. Radiation as part of the trial was not included in these studies. The role for chemo-IO vs chemo alone (with or without radiation) for high risk non-measurable uterine cancer was tested in GOG3053/KEYNOTE-B21 and was negative. In GOG3053, the radiation was delivered after the chemotherapy portion. There may be benefit in patients with dMMR subsets or p53mut. Otherwise in general chemo-IO f...

I would not give EBRT to a patient that meets the criteria for chemo-IO. There is evidence to show this could potentially decrease the TME immune cell population as well as disrupt lymphatic channels, thereby decreasing the effectiveness of IO. A recent molecular analysis (presented at SGO 2024, Clements et al.) showed no benefit and potential harm in the dMMR population of GOG258 that received EBRT.

I think although a relatively data free zone, you can consider brachytherapy for a positive vag...