Feasibility and Value of Genomic-Profiling in Cancer of Unknown Primary: Real-World Evidence from Prospective Profiling Study.

Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer of unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial of 158 patients with CUP (10/2016-09/2019) who underwent GP using next-generation sequencing designed to identify genomic alterations (GAs). Only 61 (38.6%) patients had sufficient tissue for successful profiling. GAs were seen in 55 (90.2%) patients; of which GAs with FDA approved genomically-matched therapy were seen in 25 (40.9%) cases. A change in therapy was recommended and implemented (primary endpoint of the study) in 25 (10.1%) and 4 (2.5%) patients of the entire study cohort, respectively. Most common reason for inability to implement the profiling-guided therapy was worsening of performance status (56.3%). Integrating GP in management of CUP is feasible but challenging due to paucity of tissue and aggressive natural history of the disease and requires innovative precision strategies.