Clinical utility of comprehensive liquid molecular profiling in patients with advanced endometrial cancer

• Published in: Cancer 2024-10, Vol.130 (19), p.3311-3320
• Main Authors: Blanc‐Durand, Félix, Camilleri, Geraldine M., Bayle, Arnaud, Aldea, Mihaela, Vasseur, Damien, Ouali, Kaissa, Michels, Judith, Pautier, Patricia, Nicotra, Claudio, Ngo‐Camus, Maud, Lacroix, Ludovic, Rouleau, Etienne, Ponce‐Aix, Santiago, Italiano, Antoine, Leary, Alexandra
• Format: Article
• Language: English
• Subjects: Biopsy; Cancer; cell‐free DNA (cfDNA); clonal hematopoiesis; Customization; Disease management; DNA fingerprinting; Endometrial cancer; Endometrium; Life Sciences; Medical prognosis; Metastases; Metastasis; Microsatellite instability; Mismatch repair; molecular profile; p53 Protein; Patients; personalized treatment; Subgroups; Tumors; Uterine cancer
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35381

Background Molecular characterization has significantly improved the management of advanced endometrial cancer (EC). It distinguishes four molecular subclasses associated with prognosis and personalized therapeutic strategies. This study assesses the clinical utility of cell‐free DNA (cfDNA) profiling in EC to identify targetable alterations. Methods Women with metastatic or recurrent EC were prospectively recruited within the framework of the STING trial (NCT04932525), during which cfDNA was analyzed. Genomic alterations were identified with the FoundationOne CDx assay. Each molecular report underwent review by a molecular tumor board. Alterations were categorized via the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT). Results A total of 61 patients were enrolled. The median age was 66.9 years, with 43% presenting frontline metastatic disease. All histologic subgroups were represented. Notably, 89% of patients yielded informative cfDNA analysis. Six tumors were classified with deficient mismatch repair/microsatellite instability (11%) and 37 as TP53 gene mutant (67%), and 12 had nonspecific molecular profiles (22%). Molecular classification based on liquid biopsy showed 87.5% accuracy in correlating with tissue results. Moreover, 65% of cases exhibited ≥1 actionable alteration, including 25% ESCAT I alterations and 13% ESCAT II alterations. Consequently, 16% of patients received a molecularly matched therapy, and presented with a 56% response rate and median progression‐free survival of 7.7 months. Conclusions cfDNA sequencing in EC is a feasible approach that produces informative results in 89% of cases and accurately categorizes patients into the main molecular subclasses. It also reveals multiple actionable alterations, which offers the potential for personalized therapeutic strategies. Cell‐free DNA sequencing is a highly feasible assay that allows an accurate molecular characterization of patients with advanced endometrial cancer while detecting multiple actionable alterations. It serves as a valuable tool for tailoring the management of patients with metastatic endometrial cancer.