dostarlimab

Overview

Dostarlimab is an anti-PD-1 monoclonal antibody (immune checkpoint inhibitor) with FDA approval in dMMR/MSI-H endometrial carcinoma and dMMR solid tumors. It blocks the PD-1/PD-L1 axis to restore anti-tumor T cell activity.

Evidence in the corpus

• Black endometrial carcinoma (EC) patients are significantly less likely to harbor MSI-H or TMB-H tumors (15% vs 33% and 14% vs 25% in White patients, respectively), substantially reducing eligibility for dostarlimab and pembrolizumab immune checkpoint therapy; 22.4% of Black vs 39.7% of White EC patients had OncoKB Level 1/2/3A actionable alterations (P<0.001) PMID:37651310.
• ERBB2 amplification is more prevalent in Black EC patients (12% vs 3%), representing an alternative therapeutic opportunity with anti-HER2 agents including trastuzumab and trastuzumab deruxtecan PMID:37651310.
• In endometrial carcinoma, lenvatinib is used in combination with pembrolizumab for MSS/pMMR disease, the molecular subtype enriched in Black patients PMID:37651310.

Resistance mechanisms

• dMMR/MSI-H endometrial cancers are the primary responders to dostarlimab; pMMR/MSS disease – enriched in Black patients – is not responsive PMID:37651310.

Cancer types (linked)

• UCEC

Sources

• PMID:37651310

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