Dr Soliman on the Use of ctDNA as a Clinical Trial End Point in Endometrial Cancer

Pamela T. Soliman, MD, MPH, professor, the Department of Gynecologic Oncology and Reproductive Medicine, deputy chair, the Department and the Center Medical Director of the Outpatient Gynecology Center, The University of Texas MD Anderson Cancer Center, discusses the use of circulating tumor DNA (ctDNA) a clinical trial end point in endometrial cancer.

Soliman and colleagues explored the utility of ctDNA collected through a liquid biopsy as a translational end point in an ongoing phase 2 trial (NCT03008408) evaluating everolimus (Afinitor) and letrozole (Femara) with or without ribociclib (Kisqali) in patients with advanced or recurrent endometrial carcinoma. The goal was to assess the incidence of genetic mutations in pretreatment tissue biopsies and measure the correlation of tissue mutations with pretreatment ctDNA, and to assess change in mutational allele frequency (MAF) in ctDNA during treatment. Investigators selected a cohort of 30 patients already receiving treatment on the clinical trial and then added the liquid biopsy as a subanalysis, Soliman notes.

As part of the trial’s original protocol, all patients received a research biopsy prior to starting therapy, and the tissue was analyzed through next-generation sequencing to detect at any mutations that could serve as predictors of response to treatment. In her presentation at the 2023 Society of Gynecological Oncology (SGO) Annual Meeting on Women's Cancer, Soliman concluded that the role of ctDNA in clinical trial monitoring showed promising results, with pretreatment ctDNA correlating with baseline tumor biopsy results. Additionally, all responders who had mutations detected on pretreatment ctDNA, showed clearance or a decrease in MAF after 8 weeks of therapy.

Soliman also notes that ctDNA may be a less invasive way identify translational biomarkers for response on clinical trials.

Editor’s note: Dr Soliman reported receiving grant and research funding from Novartis, Incyte, and serving in a consulting role or on an Advisory board for Amgen, Clovis Oncology, Aadi, Eisai Pharmaceuticals, and Glaxo Smith Klein.