Circulating tumor DNA molecular profiling in rare cancer patients from the MASTER KEY Project.

Abstract

e14532 Background: In April 2017, MASTER KEY Project, composed of a prospective registry study part and a multiple clinical trials part, was established to promote treatment development for rare cancers, which is lacking standard or investigational therapeutic options. Circulating tumor DNA (ctDNA) analysis by next-generation sequencing (NGS) has provided new insight into personalized medicine in a more accessible, non-invasive manner; however, most reports are focused on common cancers. We report genetic alterations detected by ctDNA NGS analysis in rare solid cancers. Methods: Prospectively consented patients (pts), also enrolled in MASTER KEY registry study, had ctDNA NGS testing at a CLIA-certified lab (Guardant360) for point mutations, indels, copy number amplifications, fusions, and microsatellite instability. Alterations were assessed for incidence according to cancer type, functional impact, therapeutic implications, and comparison with tissue NGS. Main inclusion criteria: 1) age ≥16, 2) histological diagnosis of rare cancer (annual incidence less than 6 cases per 100,000 population), cancer of unknown primary (CUP), or rare tissue subtypes of common cancers, 3) active metastatic / unresectable cancer, 4) a written consent. Results: From Nov. 2018 to Jan 2019, 50 pts had Guardant360 testing. Diseases included: soft tissue sarcoma (28), ovarian carc. (7), CUP (4), salivary gland tumor (3), thyroid carc. (2), GIST (1), adrenal cortical carc. (1), rare subtype of GI tract (1), malignant mesothelioma (1), nephroblastoma (1), NET (1), NUT carc. (1). All Japanese, male/female = 14/36, median age 61, ECOG performance status 0/1/2/3 = 30/19/0/1. 76% of pts (38/50) had ≥1 alteration detected, with median number of 2 alterations (range: 0-9), with VAF(0.1-60.3%); 87%(33/38) of those pts had a variant most likely pathogenic; 61% (20/33) of those pts had a variant potential for clinical action. Mean TAT was 10.3 days. 19 pts had tissue NGS testing and in 3 pts, alterations were detected by ctDNA NGS but not by tissue NGS. Updated results of 100 patients will be presented at the conference. Conclusions: Most rare cancer patients with advanced disease had a detectable genomic alteration by Guardant360. Clinical trial information: UMIN000034394.