Personalized Therapy Selection by Integration of Molecular Cancer Classification by the 92-Gene Assay and Tumor Profiling in Patients With Cancer of Unknown Primary.

Abstract

Cancer of unknown primary (CUP) is a syndrome comprising metastatic cancers without a clinically identified primary site. Although patients with CUP have an unfavorable prognosis, treatment with site-specific therapies guided by clinical features, standard pathology, and molecular assays can improve overall survival. The 92-gene assay (CancerTYPE ID) is a gene expression-based classifier that helps identify the tissue of origin for metastatic cancers with unknown or uncertain diagnoses. This study reports the frequency of selected molecular aberrations of oncogenes, including <i>KRAS</i>, <i>IDH1/2</i>, <i>BRCA1/2</i>, and <i>BRAF</i>, in patients with CUP in the MOSAIC database to highlight potential treatment options. MOSAIC is a database of patients with CUP submitted for CancerTYPE ID testing and NeoTYPE biomarker testing. Tumor biopsy samples were analyzed by CancerTYPE ID for tumor type identification and further tested for molecular aberrations of oncogenes, including <i>KRAS</i>, <i>IDH1/2</i>, <i>BRCA1/2</i>, and <i>BRAF</i>. CancerTYPE ID identified a specific tumor type in 92.5% (2,929 of 3,168) of CUP cases in the MOSAIC database. The most commonly identified histological type was adenocarcinoma (75.4%), with pancreaticobiliary being the most common molecularly diagnosed cancer (24.9%). Aberrations in <i>KRAS</i>, <i>IDH1/2</i>, <i>BRCA</i>, and <i>BRAF</i> genes were identified in 18.8% (n = 597) of biopsies. A cancer-specific US Food and Drug Administration (FDA)-approved or investigational targeted therapy was potentially available for 24.6% (n = 147) of these patients. This retrospective analysis supports incorporating CancerTYPE ID into the evaluation for patients with CUP to help determine the tissue of origin and identify actionable genetic alterations. This approach may allow more patients with CUP to benefit from site-specific FDA-approved targeted therapies or enrollment into clinical trials.