Baseline mutational profiles of patients with carcinoma of unknown primary origin enrolled in the CUPISCO study.

BACKGROUND: Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of ∼1 year or less, stressing the need for more tailored treatments, which are currently being tested in clinical trials. CUPISCO (NCT03498521) was a phase II randomized study of targeted therapy/cancer immunotherapy versus platinum-based chemotherapy in patients with previously untreated, unfavorable CUP, defined as per the European Society for Medical Oncology guidelines. We present a preliminary, descriptive molecular analysis of 464 patients with stringently diagnosed, unfavorable CUP enrolled in the CUPISCO study. MATERIALS AND METHODS: Genomic profiling was carried out on formalin-fixed, paraffin-embedded tissue to detect genomic alterations and assess tumor mutational burden and microsatellite instability. RESULTS: Overall, ∼32% of patients carried a potentially targetable genomic alteration, including PIK3CA, FGFR2, ERBB2, BRAFV600E, EGFR, MET, NTRK1, ROS1, and ALK. Using hierarchical clustering of co-mutational profiles, 10 clusters were identified with specific genomic alteration co-occurrences, with some mirroring defined tumor entities. CONCLUSIONS: Results reveal the molecular heterogeneity of patients with unfavorable CUP and suggest that genomic profiling may be used as part of informed decision-making to identify the potential primary tumor and targeted treatment options. Whether stringently diagnosed patients with unfavorable CUP benefit from targeted therapies in a similar manner to those with matched known primaries will be a key learning from CUPISCO.

Healthcare Costs Before and After Diagnosis of Cancer of Unknown Primary Versus Ovarian Cancer in Australia.

BACKGROUND: Little is known about the healthcare resource usage and costs for patients with cancer of unknown primary (CUP). OBJECTIVE: The aim of this study was to describe and quantify healthcare resource use and costs in Australia, 6 months prior to and after a diagnosis of CUP, and compare to those of women with ovarian cancer. METHODS: Individual-level data combining baseline surveys, clinical records and Medicare Benefits Schedule (MBS) claim records were analysed for 149 patients with CUP and 480 patients with ovarian cancer from two prospective cohort studies. MBS data were aggregated for the period 6 months prior to diagnosis date and 6 months after diagnosis. Data included doctor consultations, pathology, diagnostics, therapeutic procedures, imaging, allied health and medicines. Generalised linear models were used to evaluate the cost differences between CUP and ovarian cancer using gamma family and log link functions. Models were adjusted for age, employment, marital status, surgery, chemotherapy and number of comorbidities. RESULTS: The mean healthcare costs in the 6 months prior to diagnosis of CUP were Australian (AU) $3903 versus AU$1327 for ovarian cancer (adjusted cost ratio 2.94, 95% confidence interval [CI] 2.08-4.15). Mean healthcare costs 6 months post-diagnosis were higher for patients with CUP versus ovarian cancer (AU$20,339 vs AU$13,819, adjusted cost ratio 1.47, 95% CI 1.13-1.92). Higher costs for patients with CUP were driven by imaging (AU$1937 vs AU$1387), procedures (AU$5403 vs AU$2702) and prescribed medicines for all conditions (AU$10,111 vs AU$6717). CONCLUSIONS: Pre-diagnosis costs for patients with CUP are nearly triple those for ovarian cancer. Six months after diagnosis, healthcare costs for CUP remained higher than for ovarian cancer due to imaging, procedures and medicines.