The profiling of gene expression and gene alterations by next-gen sequencing (NGS) for predicting primary tumor sites and guiding molecularly targeted therapies have been known to improve the clinical outcomes of cancer of unknown primary site (CUP). However, there’s no evidence that supports this ideology. This study aims to evaluate the clinical use of molecularly targeted therapy-based treatments for patients with CUP.

This phase 2 clinical trial included a total of 97 previously untreated patients with a favorable subset of CUP. Eligible patients had a diagnosis of unfavorable CUP after mandatory examinations. RNA and DNA sequencing was performed in all the patients. The primary outcome of the study was 1-year survival probability, along with progression-free (PFS) and overall survival (OS).

The most commonly predicted cancer types were lung (21%), liver (15%), kidney (15%), and colorectal (12%) cancer. Besides, TP53, KRAS, and CDK2NA were the most frequent gene alterations. The 1-year survival probability was 53.1%, with median OS and PFS being 13.7 months and 5.2 months, respectively. 5.2% of patients with predicted non-small cell lung cancer had targetable EGFR mutations.

The research concluded that molecularly targeted therapy-based site-specific treatment resulted in positive outcomes in patients with CUP.