Ovarian cancer is the fifth leading cause of cancer-related female mortality and the most lethal gynecological cancer. In this report, we present a rare case of recurrent granulosa cell tumor (GCT) of the ovary. We describe the case of a 26-yr-old woman with progressive GCT of the right ovary despite multiple lines of therapy who underwent salvage therapy selection based on a novel bioinformatical decision support tool (Oncobox). This analysis generated a list of potentially actionable compounds, which when used clinically lead to partial response and later long-term stabilization of the patient's disease.

e13143 Background: Anticancer Targeted Drugs (ATDs) specifically target one or a few types of tumor-related molecules in a cell. More than two hundred of ATDs were approved worldwide. They have different mechanisms of action and are effective for different cohorts of patients. However, many individual cases remain poorly responsive and it is of great importance to identify predictive markers of ATD efficacy. Our aim was to develop a platform enabling smart selection of the most efficient ATD therapies. Methods: We generated a second-opinion platform for clinical oncologists termed Oncobox. It is based on the analysis of gene expression profile of a cancer sample in comparison with the corresponding normal tissue biosamples in order to personalize selection of targeted drugs for individual cancer patients. Based on RNA-seq gene expression data, pathway activation levels are calculated and along with the concentrations of molecular target genes products used as predictors of tumor response to ATDs. Results: The Oncobox method was tested first on the retrospective samples of advanced tumors: gastric, renal cell, ovarian and colorectal cancers, thus showing ROC AUC values > 0.7. In currently ongoing prospective trial for advanced solid tumor patients, the Oncobox tests were completed for 239 patients, primary feedback information received for 144 patients. 25 patients (17%) died before prescription of the therapy, 19% received palliative care treatment, 39% received Oncobox-recommended therapies and 25% received other therapies (February 2019). Tumor responses were estimated for 30 patients (breast, colorectal, ovarian and other cancers) receiving therapies, with disease control rate of 71% for Oncobox-recommended ATDs (Bevacizumab, Crizotinib, Trastuzumab and others) and 44% for other therapies. Our results also suggest that cancer metastases and primary tumors may have different gene expression, molecular pathway activation and drug scoring patterns, thus pointing to the importance of testing multiple tumor sites. Conclusions: Our study suggests that profound analysis of gene expression profiles of tumor tissues may be useful for ATDs treatment of advanced and metastatic cancers. Clinical trial information: NCT03724097.

e13676 Background: Analysis of mutation profiles in cancer patients does not provide clinical benefits in 80-90% of cases in the US (Marquart et al., 2018). Gene expression analysis potentially complements standard detection of clinically relevant mutations. Methods: 239 adult late-stage cancer patients. RNA gene expression sequencing completed on solid tumor samples using FFPE blocks. Patient mRNA profiles were analyzed using Oncobox bioinformatics, prioritizing target drugs according to their personalized predicted efficacy. Summary reports were provided to oncologists and resulting treatment selection and outcomes were assessed. Results: As of February 2020, feedback was received from participating doctors for 224 patients; 34 patients died before therapy prescription, 52 patients received treatment other than targeted therapy (chemo, surgery, radiation, or palliative care), 75 patients received at least one targeted therapy (single or combination therapy) predicted to be effective based on Oncobox analysis (“RNAseq cohort”). 63 patients received chemo or other drug therapy predicted to be potentially ineffective from Oncobox analysis (“other cohort”). Therapeutic response was obtained on 46 patients with biopsies collected no longer than 6 months prior to analysis who had no further surgery (30 in the RNAseq cohort and 16 in the other cohort). 63% of the RNAseq cohort obtained either partial response or stable disease using Oncobox guided therapies, compared to 44% of the other cohort (19% increase of disease control). The RNAseq cohort had higher mean prior therapies (1.3) compared to the other cohort (0.8) indicating more advanced disease. The similarly designed WINTHER trial reported ~8% increase of disease control using gene expression-guided vs mutation-guided therapeutics in a cohort of advanced cancer patients averaging three prior therapies (Rodon et al., 2019). Conclusions: Collectively these data suggest that gene expression profiling provides a more clinically relevant therapeutic match, and better response rates, than mutation guided therapeutic treatments. This potentially results in improved clinical outcomes for cancer patients. Clinical trial information: NCT03724097.

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