In the GARNET trial, investigating dostarlimab monotherapy in patients with advanced and recurrent solid tumours that have progressed after platinum-based chemotherapy, an ORR of 43.5% was observed in patients with dMMR/MSI-H EC.¹ In the KEYNOTE-158 trial investigating pembrolizumab monotherapy in patients with previously treated advanced tumours, an ORR of 48% was observed in patients with dMMR/MSI-H EC.²

Abbreviations
dMMR, mismatch repair deficient; EC, endometrial cancer; MSI-H, microsatellite instability-high; ORR, objective response rate.

References

1. Oaknin A, et al. J Immunother Cancer. 2022;10:e003777.
2. O’Malley DM, et al. J Clin Oncol. 2022;40:752–61.

Pembrolizumab, durvalumab or dostarlimab in combination with carboplatin/paclitaxel all have approved indications for the first-line treatment of adult patients with primary advanced or recurrent EC,^1–3 with progression-free survival being particularly pronounced in those with dMMR/MSI-H tumours.⁴ Pembrolizumab and dostarlimab as monotherapy have approved indications for the treatment of patients with advanced or recurrent EC, who have disease progression on or following prior treatment with a platinum-containing therapy.^1,3 Pembrolizumab, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent EC in adults who have disease progression on or following prior treatment with a platinum-containing therapy.¹ Tamoxifen is currently one of the mainstays for treating hormone receptor–positive BC. Tamoxifen use is a significant risk factor related to the incidence of EC in patients with BC.⁵

Abbreviations
BC, breast cancer; dMMR, mismatch repair deficient; EC, endometrial cancer; MSI-H, microsatellite instability-high.

References

1. EMA. Pembrolizumab SmPC. Available at: https://bit.ly/3PvRLeN (accessed 18 March 2025).
2. EMA. Durvalumab SmPC. Available at: https://bit.ly/41esZWy (accessed 18 March 2025).
3. EMA. Dostarlimab SmPC. Available at https://bit.ly/3vnfGpR (accessed 18 March 2025).
4. Bogani G, et al. Ann Oncol. 2024;35:414–28.
5. Ghanavati M, et al. Cancer Rep (Hoboken). 2023;6:e1806

ICI therapy can generally continue in the presence of mild irAEs with close monitoring. However, moderate to severe irAEs may be associated with life-threatening declines in organ function and QoL, and fatal outcomes have been reported; hence, these toxicities require early detection and proper management, including administration of corticosteroids or treatment discontinuation. ICI-related pneumonitis is an uncommon but potentially serious toxicity observed with ICI therapy. Presenting symptoms related to immune therapy–induced pneumonitis may include new or worsening cough, shortness of breath, increased oxygen requirement, chest pain and/or fever. The median time to onset of pneumonitis is 34 weeks but can range from 1.5 to 127 weeks.

Abbreviations
ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; QoL, quality of life.

Reference
Schneider BJ, et al. J Clin Oncol. 2021;39:4073–126.

For grade 2 hepatic toxicities (asymptomatic [AST or ALT >3.0 to ≤5x ULN and/or total bilirubin >1.5 to ≤3x ULN]) ICI therapy should be temporarily suspended. Steroids may be administered if no improvement is seen after 3–5 days, and the frequency of monitoring should be increased to every 3 days. ICI treatment can be resumed when toxicity reverts to grade 1. Dose reductions of ICI therapy during treatment should be avoided.

Abbreviations
ALT, alanine transaminase; AST, aspartate aminotransferase; ICI, immune checkpoint inhibitor; ULN, upper limit of normal.

Reference
Schneider BJ, et al. J Clin Oncol. 2021;39:4073–126.

The phase III DUO-E trial demonstrated that carboplatin/paclitaxel plus durvalumab, followed by maintenance durvalumab with or without the PARP inhibitor olaparib, had a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent EC.¹ The phase III DOMENICA trial aims to evaluate the effectiveness of chemotherapy alone vs dostarlimab monotherapy in the first-line advanced/metastatic setting in patients with dMMR/MSI-H EC.²

Abbreviations
dMMR, mismatch repair deficient; EC, endometrial cancer; MSI-H, microsatellite instability-high; PARP, poly (ADP-ribose) polymerase; PFS, progression-free survival.

References

1. Westin SN, et al. J Clin Oncol. 2024;42:283–99.
2. Joly F, et al. J Clin Oncol. 2023;41(Suppl. 16):TPS5630.