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Study showing feasibility and possible improvements in DFS with chemo + pembro vs. chemo alone in the adjuvant setting of resected endometrial cancer in dMMR patients. While a nice idea / proof of principle, I would be more interested in how IO alone performs vs. chemo in this setting, particularly if a brief course of neoadjuvant IO is given prior to surgery.

For patients with local recurrences of endometrial cancer, XRT alone is extremely effective, and the addition of cisplatin does not offer any benefit while increasing toxicity. These patients with low-grade and vaginal recurrences have a good prognosis and most should be treated with XRT alone.

Initial results from the DUO-E study in metastatic endometrial cancer. The preliminary report suggests that maintenance durvalumab and maintenance durvalumab + olaparib were superior to standard observation after systemic carbo/taxol. As the trial data matures, the question will be: is this in all patients or driven by those with dMMR or HDR mutations?

This is another possibility for maintenance therapy. It will require further study.

An interesting study where the authors performed a post hoc analysis of randomized trials using molecular classification of endometrial cancers. There was good evidence to omit RT for those with POLE mutations and def-MMR. There seems to be a higher degree of benefit in those with a p53 mutation.

Large phase III study of carbo/taxol+pembro x 6 followed by pembro alone x 14 cycles in metastatic endometrial cancer. There was a benefit in both pMMR and dMMR patients, although the magnitude was unsurprisingly higher in those with dMMR. OS results are still pending, and carcinosarcoma-type histology was excluded. This combination has been approved and is on NCCN as a cat-1 recommendation.

Chemo + IO may become the SOC for 1L treatment of met-endometrial adenoCa. For pembro + chemo, there was a 70% lower risk of disease progression in dMMR and a 46% lower risk in pMMR compared to placebo + chemo. For pMMR patients, the impact on 2L therapy responses will need to be considered carefully, as lenvantinib + pembro has been found to be superior to either agent alone after chemo.

Chemo + IO may become the SOC for 1L treatment of met-endometrial adenoCa. For dostarlimab + chemo, there was an OS at 24 months of 83 vs. 58% in the dMMR and 67% vs. 55% in the pMMR groups compared to placebo + chemo. The question remains if chemo + IO is superior to IO alone in dMMR patients.

Another prognostic marker that can predict added efficacy of therapy in this case bevacizumab.