Abstract 43: Clinical implications of real-world data on plasma circulating tumor DNA in gynecologic cancer patients

Abstract

Abstract Molecular characterization of individual cancers is increasingly important in dictating prognostic factors and directing therapy. Next-generation sequencing of blood-derived circulating tumor DNA (ctDNA) offers less invasive, more convenient collection and a more real-time representation of a tumor and its molecular heterogeneity than tissue-based analysis. However, little is known about the clinical implications of ctDNA assessment in gynecologic cancer. We report the clinicopathologic and genomic information for 105 gynecologic cancer patients with ctDNA analysis, including 78 patients with tissue-based sequencing, who were enrolled in Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT, NCT02478931). Tumors in our cohort included ovarian (47.6%), uterine (35.2%), cervical (12.4%), vulvar or vaginal (2.9%), and gynecologic cancer of unknown primary (1.9%). The majority of patients (74.3%) had at least one characterized alteration on ctDNA analysis. The most common alterations were in the following genes: TP53 (N=59, 56.2% of patients), PIK3CA (N=26, 24.8%), KRAS (N=14, 13.3%), BRAF (N=10, 9.5%), ERBB2 (N=8, 7.6%), and MYC (N=8, 7.6%). Higher total percentage of ctDNA was associated with worse overall survival (HR 2.18, p=0.008), and therapy matched to ctDNA genomic alterations (N = 33 patients) independently predicted improved overall survival (HR 0.34, p=0.007) as compared to unmatched therapy (N = 28 patients). Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. This study provides evidence for the utility of ctDNA in determining outcome and individualizing cancer therapy in patients with gynecologic cancer. Citation Format: Lindsey Michelle Charo, Ramez N. Eskander, Ryosuke Okamura, Sandip Patel, Mina Nikanjam, Richard Layman, David E. Piccioni, Shamei Kato, Michael McHale, Razelle Kurzrock. Clinical implications of real-world data on plasma circulating tumor DNA in gynecologic cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 43.