Controversies in the Management of Mesonephric and Mesonephric-Like Adenocarcinomas of the Female Genital Tract.

Mesonephric and mesonephric-like adenocarcinomas of the gynecologic tract are a rare subset of gynecologic tumors that are frequently associated with the presence of somatic KRAS mutations. Owing to their rare nature and ability to arise in different gynecologic sites, pathologic diagnosis is often challenging and under-represented. Immunohistochemistry and routine use of next-generation sequencing has allowed these cases to be more readily identified; however, there is still a paucity of clinical outcomes data, and the efficacy of treatment paradigms remains largely unknown. Historically, mesonephric and mesonephric-like adenocarcinomas were considered to be less responsive to systemic treatment, but response rates to first-line platinum-doublet chemotherapy for metastatic disease may be higher than initially suspected. Recurrent disease is often distant and located in the lungs, suggesting an important role of surveillance chest imaging. Given that most of these tumors are associated with somatic mitogen-activated protein kinase pathway mutations, a currently open phase II trial is assessing the dual RAF/MEK clamp avutometinib in combination with the FAK inhibitor defactinib in patients with recurrent mesonephric and mesonephric-like adenocarcinomas. Continued multi-institutional prospective trials are necessary to elucidate additional treatment options for these rare tumors.
Competing Interests: Declaration of Competing Interests CA reports Clinical Trial funding paid to institution from AbbVie – MSKPI – GOG 3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator and MSK PI, DO81RC00001; ENGOT-ov46; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, ARIEL 2 &3; Genentech/Roche – MSK PI, GOG3015 (IMagyn050). She also participates on an advisory board for Blueprint Medicine – advisory board June 30, 2021 (no consulting fee); Merck – Global Cervical and Ovarian Cancer virtual advisory board July 10, 2023 (no consulting fee); and AstraZeneca – AZ Evolve dmc April 26, 2023 to present. She also serves on the GOG Foundation, Board of Directors (unpaid, occasional travel cost reimbursement to attend meetings), and NRG Oncology Board of Directors (unpaid). RG reports honoraria from GlaxoSmithKline, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. The remaining authors report no competing interests.
(Copyright © 2025 European Society of Gynaecological Oncology and the International Gynecologic Cancer Society. Published by Elsevier Inc. All rights reserved.)