Ovarian Epithelial Tumor (OVT)

Overview

Ovarian epithelial tumor (OVT) is the broad OncoTree category for epithelial ovarian malignancies, encompassing high-grade serous (HGSOC), low-grade serous, endometrioid, clear cell, and mucinous carcinomas, as well as ovarian/fallopian tube/peritoneal primaries. It sits under OVARY in OncoTree.

Cohorts in the corpus

  • Part of the 35-patient phase 2 trial of nivolumab in dMMR/MSI-H or hypermutated gynecologic cancers (NCT03241745) at MSK; OVT patients included alongside UCEC. Dataset: ucec_msk_2024. PMID:38653864

Recurrent alterations

  • MLH1, MSH2, MSH6, PMS2 — dMMR/MSI-H status (via MMR gene mutations or MLH1 promoter hypermethylation) defines eligibility for immune checkpoint therapy in the OVT context. PMID:38653864
  • SETD1B — mutations associated with response to nivolumab (58% responders vs. 14% non-responders, P=0.015). PMID:38653864
  • MEGF8 — mutations enriched in nivolumab responders (32% vs. 0%, P=0.027). PMID:38653864

Subtypes

  • dMMR/MSI-H ovarian cancers included in the nivolumab phase 2 trial; dMMR mechanism (genetic vs. epigenetic) was not associated with differential response (P=0.43). PMID:38653864

Therapeutic landscape

  • Nivolumab in dMMR/MSI-H gynecologic cancers (UCEC and OVT combined): ORR 58.8%, PFS24 64.7%, median PFS 21.6 months. TMB and PD-L1 expression were not predictive of response within dMMR-selected populations. PMID:38653864
  • T cell functional states (dysfunctional CD8+PD-1+ and terminally dysfunctional CD8+PD-1+TOX+ T cells) and spatial proximity to PD-L1+ cells predict clinical benefit (AUC=0.897, P=0.0007). PMID:38653864

Sources

  • PMID:38653864 — Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses (Nature Medicine, 2024)

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