Elsevier

Gynecologic Oncology

Volume 156, Issue 3, March 2020, Pages 552-560
Gynecologic Oncology

Therapeutic options for mucinous ovarian carcinoma

https://doi.org/10.1016/j.ygyno.2019.12.015Get rights and content
Under a Creative Commons license
open access

Highlights

  • MOC often carry genetic events indicating a targeted therapy and should be entered in basket trials of such agents.

  • A distinct subset of MOC are estrogen receptor positive (~11%), suggesting hormonal therapy as an option.

  • Mismatch repair deficiency is present in <1% of MOC; the role of checkpoint inhibitors is uncertain.

  • Rarity of homologous recombination deficiency means MOC is unlikely to respond to platinum-based therapy/PARP inhibitors.

Abstract

Objective

Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents.

Methods

We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117–166).

Results

Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184).

Conclusions

Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition.

Keywords

Ovarian cancer
Precision oncology
Molecular targeted therapy
Therapy
Sequencing
Genomic

Cited by (0)

GAMuT collaborators (non-author contributors): Michael S Anglesio, George Au-Yeung, Alison Brand, Georgia Chenevix-Trench, Stephen B Fox, Neville F Hacker, Tom W Jobling, David G Huntsman, Anne-Marie Mes-Masson, Linda Mileshkin, Diane M Provencher, Kurosh Rahimi, Goli Samimi, Raghwa Sharma.

1

Equal first author contribution.

2

Equal senior author contribution.