Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer.

ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer (EC). A de-identified retrospective analysis of 1988 patients with advanced/recurrent EC was performed. In addition, an analysis of a real-world evidence (RWE) cohort was completed (n=1266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA. Among 1988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n=1821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%) and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%) and EGFR (19.3%). From the RWE cohort, those with TP53 mutations had a worse overall survival (OS) vs those without TP53 mutations (p=0.02) and those with TP53 co-mutations had an inferior OS in comparison to TP53-mutated only (p=0.016). Amongst these, patients with a PIK3CA co-mutation (p=0.012) and CCNE1 amplification (p=0.01) had inferior OS compared to those with only TP53 mutations. 57 patients with newly diagnosed EC had at least 2 serial ctDNA samples showing evolution in detected variants compared to baseline samples, with TP53 being the most frequent change. This study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.