Following the Keynote B21 trial, clinicians have become more selective with adjuvant immunotherapy in endometrial cancer. The study showed minimal benefit for pMMR patients and less impressive gains overall in its lower-risk population compared to advanced disease trials. This has led to a practice of reserving adjuvant chemo-IO primarily for stage 3 dMMR patients.

Potent responses to chemo-immunotherapy are promoting a shift toward neoadjuvant treatment for advanced endometrial cancer. Waiting six cycles often achieves a response sufficient to allow for a minimally invasive hysterectomy instead of a more extensive primary debulking surgery.

Despite lacking direct comparative trials in endometrial cancer, some oncologists prefer PD-1 inhibitors (like pembrolizumab) over PD-L1 inhibitors. This preference stems from observing higher single-agent activity in smaller studies and a clinical belief that PD-1s may be more potent for this specific cancer.

While chemo plus immunotherapy showed a benefit in MS-stable patients, it's not curative. The expert predicts clinicians may shift away from using it universally upfront, potentially favoring other agents first for this non-curative but beneficial therapy.

Clinical trials show a sustained overall survival benefit for upfront chemo-immunotherapy in dMMR patients, even with over 90% of the placebo group receiving immunotherapy upon progression. This demonstrates that delaying immunotherapy fails to rescue outcomes, making upfront use critical.

For endometrial or cervical cancer patients who progress after receiving a checkpoint inhibitor, re-challenging with a single-agent immunotherapy is a less desirable approach. Emerging data suggests that a combination therapy—such as an ICI paired with a TKI like lenvatinib or a bispecific antibody—offers a more promising chance of response.

With dostarlimab, pembrolizumab, and durvalumab showing similar efficacy in endometrial cancer, the final selection often depends on non-clinical factors like clinician familiarity, specific trial criteria, or insurance company mandates.

Even in elderly or frail patients with MSI-high endometrial cancer, the rapid and effective tumor response from combination chemotherapy and immunotherapy often improves quality of life so significantly that it's the preferred approach over single-agent IO.

Disparate clinical trial results in endometrial cancer suggest a mechanistic difference between immunotherapy targets. PD-1 inhibitors (dostarlimab, pembrolizumab) have shown pronounced responses, whereas the PD-L1 inhibitor atezolizumab did not, indicating that targeting the PD-1 receptor may be a more robust strategy in GYN cancers.