Clinical utility of comprehensive genomic profiling for patients with cancer of unknown primary site

Cancer of unknown primary site (CUP) has metastatic lesions, but the origin of the cancer cannot be determined despite extensive examinations. CUP accounts for 2-3% of solid cancer diagnoses. Although most patients with CUP receive empirical chemotherapy such as carboplatin plus paclitaxel, they have poor prognoses; the median OS is less than 12 months. We investigated whether comprehensive genomic profiling (CGP) based on next-generation sequencing (NGS) of tumor DNA are useful for improving clinical outcomes. Since we started CGP tests at TMDU, a total of 13 patients who were diagnosed with CUP underwent CGP. We retrospectively investigated the results of their CGP, treatment, prediction of the primary site, and the therapeutic efficacy. 13 patients underwent CGP: F1CDx (10), Guardant360 (3), and NCC Oncopanel (1), respectively; there is one overlapping. The median age was 65 (range: 37-80) years; 5 out of 13 were men. Of the 13, 6 were adenocarcinomas and 7 were non-adenocarcinomas, which included 3 squamous cell carcinomas and 4 carcinomas (NOS). Within these 14 CGP tests, a total of 73 mutations and 117 VUSs were identified. There were 2 patients with TMB-High. All cases harbored at least 1 actionable mutation. The most common detected mutations included TP53, CDKN2A, FGFR1, ARID1A, and PIK3CA. We predicted the primary site in the following 6 patients via multidisciplinary molecular tumor board (MTB): 2 HNSCCs, 3 lung cancers, and 1 ovarian cancer. Of the 7, a patient with ALK fusion was treated with alectinib; the patient achieved complete response for almost 3 years. Another patient with TMB-High and SMARCA4 mutation was treated with nivolumab. This patient also achieved notable response for over 2 years. The prognosis of CUP is generally poor. However, multidisciplinary MTB are useful to predict the primary site and select targeted therapy and thus CGP might improve a clinical outcome of CUP.