Integrating comprehensive cancer genome profiling into clinical practice in an Italian referral center: Results of the first year of the fpg500 programme

The comprehensive cancer genome profiling (CGP) programme (ID: FPG500, IRB approval 3837) is an interventional monocentric study extending somatic genomic assessment to 523 genes in patients with advanced solid tumors. The study enrolls cancer patients whose molecular characterization should be warranted according to national and international guidelines. The primary endpoints were the feasibility of the programme (turn around time-TAT and samples failure rate) and the rate of actionable alterations identified. Secondary endpoints included the number of reports sent to the institutional molecular tumor board (MTB), the rate of patients’ enrollment in biomarker-driven clinical trial and the identification of potentially germline variants. From January 2022 to December 2022, 1367 patients were enrolled, including non-small-cell lung cancer (263), ovarian (446), endometrium (246), colorectal (191), pancreatic (83), cholangiocarcinoma (28), prostate (48), melanoma (45), gastrointestinal stromal tumor (GIST) (3), thyroid (7) and breast cancer (7). The overall failure rate was 5%. CGP sequencing data were available for 1162 (85%) patients, while 205 (15%) were addressed to targeted panels. By the end of 2022 an improving average TAT of genomic profiling was reported (25 days), despite an increasing number of monthly analysed samples (mean 114). Genomic alterations according to OncoKB annotation were identified in 96% patients. Potentially pathogenic/likely pathogenic germline variants were identified in 29% of patients. Overall, 6% of cases were sent to MTB. FPG500 represents the largest prospective European single institution genomic profiling series and highlights the utility of CGP for identifying therapeutic targets in selected cancer patients, concomitant alterations for further predictive and prognostic characterization and germline implications.