Uncommon Cancers, Common Challenges: A Review of Progress and Gaps in Rare Gynecologic Malignancies

Uncommon Cancers, Common Challenges: A Review of Progress and Gaps in Rare Gynecologic Malignancies is a CME/CE-accredited educational activity designed to strengthen clinicians’ understanding of the clinical, histologic, and molecular characteristics of rare gynecologic malignancies. The program addresses key challenges in the diagnosis, prognostic assessment, monitoring, and treatment of adult granulosa cell tumors (aGCT), low-grade serous ovarian cancer (LGSOC), and mesonephric-like adenocarcinoma (MLA), with emphasis on the role of molecular profiling in guiding treatment decisions.

The activity includes an eMedSurvey to assess baseline knowledge, competence, performance, and perceptions, followed by an expert-led 45-minute session featuring Dr. Rachel Grisham, MD, Section Head of Ovarian Cancer at Memorial Sloan Kettering Cancer Center. The session explores the molecular and clinical features of rare ovarian cancers, including FOXL2 mutations in aGCT, MAPK pathway alterations in LGSOC, and the clinical characteristics of MLA. It reviews treatment approaches for recurrent disease, including cytoreductive surgery, endocrine therapy, MEK inhibitors, and the combination of avutometinib and defactinib. The presentation also examines the mechanism of action and clinical evidence for avutometinib and defactinib, the ENGOT-ov60/GOG-3052/RAMP 201 study, the FDA accelerated approval pathway, ctDNA testing considerations, and emerging targeted treatment strategies. This enduring webcast is a recording of the live HerHealth 2026 session and is available on the eMedEd and eMedEvents platforms. Educational impact will be evaluated using Moore’s expanded outcomes framework, assessing declarative and procedural knowledge (Levels 3a and 3b), competence (Level 4), and performance (Level 5), including follow-up measures through eMedPerformance.

The initiative aims to improve the integration of histologic and molecular findings into clinical decision-making for rare gynecologic malignancies. Through evidence-based updates on emerging therapies, clinical trial results, and treatment pathways, the program seeks to support individualized treatment selection, appropriate monitoring, and improved management of patients with these uncommon cancers.

Learning Objectives:
LO-1: Describe the features and molecular profile of rare forms of ovarian cancer including granulosa cell tumor, low grade serous ovarian cancer and mesonephric-like cancer

LO-2: Describe the approval pathway for the first drug FDA approved for treatment of recurrent low grade serous ovarian cancer patients

LO-3: Describe the mechanism of activity and activity of avutometinib and defactinib