Therapy alteration of solid tumors based on FoundationOne comprehensive genome profiling assay.

person Kirill Karlin University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland info_outline Kirill Karlin, Abdullah Kahraman, Alessandra Curioni Fontecedro, Holger Moch, Martin Zoche, Alexander Rheinhard Siebenhuener

Authors person Kirill Karlin University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland info_outline Kirill Karlin, Abdullah Kahraman, Alessandra Curioni Fontecedro, Holger Moch, Martin Zoche, Alexander Rheinhard Siebenhuener Organizations University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland, University Hospital of Zurich, Department of Oncology, Zurich, Switzerland, Department of Pathology and Molecular Pathology, Zurich, Switzerland, University Hospital Zurich, Department of Oncology, Zurich, Switzerland Abstract Disclosures Research Funding Other Background: Molecular profiling assays are becoming widely available and provide valuable information on tumor characteristics, which can identify targeted therapies or immunotherapies for cancer patients. However, the clinical utility of such tests remains unclear. Within our institution, we analyzed the clinical utility and subsequent treatment alterations of the FoundationOne Comprehensive Genome Profiling Test (FOne). Methods: We conducted a retrospective cohort review (2017 - 2018) of patients with solid tumors under standard diagnostic care who received FOne testing. We reviewed the therapies that were proposed by FOne and studied whether they led to a therapeutic alteration. Results: 71 patients were identified, of which the majority presented a progressive disease state (80%). Among the cancer types most frequently tested were adenocarcinoma of the colon (14%), prostate (8%), lung (4%), intrahepatic cholangiocarcinoma (8%) and breast invasive ductal carcinoma (4%). In 16 cases (22%), therapies suggested by FOne were approved in patient’s tumor type while in 30 cases (42%) therapies were approved in another tumor type. For an additional 13 cases (18%) only therapies tested in clinical trials were reported. 4 patients (6%) received a new therapy based on the FOne result: cancer of unknown primary (Everolimus due to a TSC1 mutation), cutaneous angiosarcoma (Pembrolizumab due to a high tumor mutational burden (TMB)), gastrointestinal neuroendocrine carcinoma (Ipilimumab and Nivolumab due to an intermediate TMB) and mucinous adenocarcinoma of the appendix (Talazoparib due to an ATM mutation). For 11 cases (15%), a new therapy option was identified by FOne, which due to the current treatment plan might be considered for later use. 3 cases (4%) were evaluated for potential clinical trial enrollment. Note that for an additional 6 patients (8%), the therapies proposed by FOne were already established on the basis of previous testing (e.g. smaller genomic panels, IHC, FISH). Conclusions: Overall, 18 (25%) patients received a new therapy option by FOne after standard of care diagnostics. Therapeutic alterations were observed particularly in patients with a rare or unknown tumor type.