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Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC)

A Spreafico1, A M Oza1, B A Clarke2

  • 1Department of Medicine, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

Gynecologic Oncology
|January 8, 2017
PubMed
Abstract

Insights

Genomic profiling of Type I Epithelial Ovarian Cancers (EOCs) identified actionable mutations. MEK inhibitor combinations showed therapeutic promise in KRAS/NRAS-mutant EOC patients, indicating an active treatment strategy.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Type I Epithelial Ovarian Cancers (EOCs) often exhibit genomic alterations activating the MAPK signaling pathway.
  • Evaluating therapeutic responses in Type I EOC patients receiving genotype-matched therapy is crucial.

Purpose of the Study:

  • To assess treatment outcomes in Type I EOC patients undergoing genotype-matched therapy.
  • To identify actionable mutations and their therapeutic implications in Type I EOC.

Main Methods:

  • Prospective molecular profiling of tumor tissues using MALDI-ToF mass spectrometry or targeted sequencing.
  • Retrospective review of treatment outcomes on genotype-matched trials using RECIST v1.1 and CA125 criteria.

Main Results:

  • Molecular profiling of 55 Type I EOC patients revealed somatic mutations in 64%, including KRAS, NRAS, and PIK3CA.
  • Fifteen patients received genotype-matched therapy; 14 with KRAS/NRAS mutations were treated with MEK inhibitor combinations.
  • Among evaluable patients, 7 achieved partial response and 7 had stable disease; 10/10 KRAS/NRAS mutant patients showed CA125 response.

Conclusions:

  • Genotyping and targeted sequencing of Type I EOCs frequently identify actionable mutations.
  • MEK-based combination therapy is an active strategy for KRAS/NRAS-mutant Type I EOC patients.
Keywords:
MEK inhibitorMolecular profilingType I epithelial ovarian cancer

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