Table 1 The current state of checkpoint inhibitors in gynecologic carcinoma (as of May 2021).

All solid tumors

• Advanced/metastatic solid tumors are FDA-approved candidates for pembrolizumab in the setting of MMRd/MSI-H. Across solid tumors in this category, responses have been observed in 53% with complete responses in 21%^14,15.

• Advanced/metastatic solid tumors are FDA-approved candidates for pembrolizumab in the setting of high TMB on (FoundationOne assay, ≥10 mutations per megabase). 29% of high TMB solid tumors have shown response to this therapy including 4% with complete responses³².

Endometrial carcinoma

• Many advanced endometrial cancers qualify for pembrolizumab based on the FDA approval in MMRd/MSI-H solid tumors, with 78% of qualifying cases showing either response or stable disease following this therapy^14,15.

• Dostarlimab is FDA-approved for advanced MMRd endometrial cancers using a specific companion diagnostic assay (Ventana MMR Dx)³⁴.

• Pembrolizmuab is FDA-approved in combination with the VEGFR kinase inhibitor lenvatinib for recurrent/advanced endometrial cancers irrespective of biomarker status; trial data demonstrated response in 40% of patients who received this combination¹⁷.

• Trials in PD-L1-positive endometrial cancer which did not require MMRd/MSI-H showed partial response to pembrolizumab in 13% with stable disease in another 13%¹⁶.

• POLE-mutated endometrial cancers have shown complete regression following treatment with nivolumab^29,30.

Cervical carcinoma

• Pembrolizumab is FDA-approved for PD-L1-positive (CPS ≥  1) recurrent/advanced cervical carcinomas.

• The majority (~80%) of cervical squamous carcinomas and adenocarcinomas will meet the threshold for PD-L1-positivity.

• 14% of PD-L1-positive advanced tumors show some response but <3% demonstrate complete response^18,19.

• 2.6% of cervical cancers are MMRd/MSI-high and 14.9% are TMB-high, offering additional avenues for pembrolizumab access;^51,63 however, the majority of these cases would already qualify based on PD-L1 expression.

Vulvar carcinoma

• No tumor-specific FDA approvals exist.

• Responses to pembrolizumab have been reported in recurrent squamous cell carcinoma of the vulva²⁰.

Ovarian carcinoma

.• No tumor-specific FDA approvals exist.

• Up to 10% of endometrioid and clear cell ovarian carcinomas and 1–2% of ovarian serous carcinomas will qualify for pembrolizumab based on MMRd/MSI-H^49,50,51,52.

• Pembrolizumab and nivolumab have been shown to have anti-tumor activity in some cases of platinum-resistant ovarian cancer^21,22

Gestational trophoblastic tumors

• No tumor-specific FDA approvals exist.

• Avelumab provided cures for 50% of patients with chemotherapy-resistant gestational trophoblastic tumors in a recent trial²³.

Uterine sarcomas

• No tumor-specific FDA approvals exist.

• When administered as a single-agent, nivolumab did not show benefit among previously treated women with advanced uterine leiomyosarcoma²⁴.

• Trials from sarcomas across anatomic sites have shown rare cases of uterine leiomyosarcoma with therapeutic response or disease stabilization following anti-PD-1 treatment^25,26,27.