SITC Immunotherapy for the Treatment of Gynecologic Cancer Guideline Summary

Assessment and Screening

For all patients with advanced or recurrent gynecologic cancer, MMR IHC should preferentially be performed as a first-line immunotherapy biomarker for dMMR (LE:1). MSI and NGS testing can be considered as second-line immunotherapy biomarker tests (LE:3).
With the exception of cervical cancer (LE:2) (and possibly other HPV-related gynecologic cancers), PD-L1 IHC expression should not be used for clinical decision-making for patients with advanced or recurrent gynecologic cancers.
For all patients with advanced or recurrent gynecologic cancers, NGS should be considered to assess for TMB-H eligibility for pembrolizumab treatment under the tissue-agnostic indication (LE:3).
For all patients with gynecologic cancer, biomarker evaluation of recurrent lesions may be considered at the time of recurrence.
For patients with advanced/recurrent cervical cancer, PD-L1 testing is recommended (LE:2). MMR IHC and NGS for MSI and TMB can be considered (LE:3).
For patients with recurrent or metastatic cervical cancer that is PD-L1-positive (CPS≥1) and has progressed on or after chemotherapy, pembrolizumab should be considered (LE:3).
For patients with metastatic cervical cancer that is PD-L1-positive (CPS≥1), pembrolizumab with chemotherapy with or without bevacizumab should be considered (LE:2).
For patients with anti-PD-(L)1-resistant cervical cancer, currently there are no data to inform the sequencing of therapies and/or rechallenge with an ICI.

Treatment

For all patients with cervical cancer, clinical trial enrollment should be offered, as feasible. Non-FDA-approved immunotherapy combination strategies should only be considered in the context of a clinical trial.
Tumor PD-L1 expression should not be used to guide immunotherapy treatment decisions in endometrial cancer (LE:2).
For all patients with advanced or recurrent endometrial cancer, MMR IHC on tumor tissue should preferentially be performed as a first-line immunotherapy biomarker for dMMR (LE:1). MSI and NGS testing can be considered as second-line immunotherapy biomarker tests (LE:3).
For first-line treatment of recurrent or metastatic endometrial cancer, carboplatin plus paclitaxel with or without trastuzumab (if HER2+ serous endometrial cancer) was the standard of care at the time of guideline publication (LE:2). Anti-PD-1 ICIs in combination with carboplatin plus paclitaxel demonstrated statistically significant and clinically meaningful improvements in PFS over chemotherapy alone for the treatment of previously untreated stage III or IV or first recurrent (after prior neoadjuvant or adjuvant chemotherapy) endometrial cancer. The observed benefit was regardless of MMR status (LE:2).
For second-line treatment of patients with pMMR/MSS advanced or recurrent endometrial cancer, pembrolizumab plus lenvatinib is recommended, as indicated. For second-line treatment of patients with TMB-H/pMMR/MSS endometrial cancer (LE:2), pembrolizumab plus lenvatinib is the standard of care option (LE:2) however, anti-PD-1 monotherapy may also be an option (LE:3).
For patients with dMMR/MSI-H advanced or recurrent endometrial cancer who have disease progression following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation, pembrolizumab monotherapy is recommended (LE:3). For patients with dMMR/MSI-H advanced or recurrent endometrial cancer who have disease progression following prior platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation, dostarlimab monotherapy is recommended (LE:3).
For all patients with endometrial cancer, clinical trial enrollment should be encouraged, as feasible. Non-FDA-approved immunotherapy combination strategies should only be considered in the context of a clinical trial.
For all patients with ovarian cancer, clinical trial enrollment should be offered, as feasible.
NGS testing should be offered to all patients with newly diagnosed ovarian cancer (LE:2).
For patients with recurrent TMB-H and/or MSI-H/dMMR ovarian tumors with no satisfactory alternative treatment options, treatment with ICIs should be considered (LE:3).
Tumor PD-L1 expression should not be used to inform treatment decisions for ICI use in ovarian cancer (LE:2).
For all patients with rare gynecologic malignancies, clinical trial enrollment should be offered, as feasible.
For all patients with rare gynecologic malignancies, testing for TMB-H and MSI-H by NGS (preferred) and MMR by IHC (as an alternative) is recommended, for potential treatment under tissue-agnostic indications for ICIs (LE:3). For patients with rare gynecologic malignancies, testing for PD-L1 by IHC may be considered (LE:4).
For previously treated patients with recurrent or metastatic vulvar or vaginal squamous cell carcinoma, second-line treatment with pembrolizumab (for patients with PD-L1-positive/TMB-H/MSI-H/dMMR tumors) or nivolumab (for patients with HPV-related tumors) should be considered (LE:3).
For patients with unresectable/metastatic vulvar or vaginal melanoma, treatment can follow the standard of care treatment paradigms for cutaneous melanoma.
For patients with locally advanced vulvar or vaginal melanoma with high risk of recurrence, adjuvant treatment with an anti-PD-1 ICI with or without an anti-CTLA-4 ICI may be considered.
For patients with uterine sarcoma who have exhausted other treatment options, biomarker-driven (ie, dMMR, TMB-H, or MSI-H) treatment with an anti-PD-1 ICI may be considered.
For patients with previously treated rare epithelial endometrial tumors, second-line treatment with combination pembrolizumab plus lenvatinib should be considered.
For patients with recurrent GTN with prior chemotherapy treatment, treatment with an anti-PD-(L)1 ICI may be considered (LE:3).

Overview

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Immunotherapy for the Treatment of Gynecologic Cancer

Immunotherapy for the Treatment of Gynecologic Cancer

Assessment and Screening

Treatment

Overview

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Authoring Organization