ESCAT gene actionability detection in early-stage ovarian: A descriptive analysis of an Italian referral center

BackgroundAccording to ESMO guidelines, the early stages epithelial ovarian carcinoma (EOC) therapeutic algorithm is mainly driven by grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for FIGO stage IB-IC but overtreatment remains an issue. However, in contrast, individuals truly at higher risk of recurrence are not clearly identified and do not currently have access to additional therapeutic strategies. We aimed at describing potential new therapeutic targets in this setting of disease.MethodsIn January 2022 our institution launched a comprehensive cancer genome profiling (CGP) (FPG500 IRB approval 3837; NCT06020625) enrolling EOC patients, regardless of stage and histology except for mucinous and borderline tumors. Oncogenic and likely oncogenic alterations were reported according to OncoKB and classified as Tier I-II-III according to ESCAT classification. The aim of the current analysis was to describe ESCAT gene actionability findings.ResultsFrom January 1st 2022 to 31st December 2023, 194 patients with EOC FIGO stage I-II were enrolled. Overall, 130 patients (68%) had at least one tier I-III ESCAT alteration. In low-grade histotypes (57 pts), the more frequent tier I-III variants were in PIK3CA (56%), PTEN (25%) and BRAF V600E (5%). In CC (48pts), the frequency of PIK3CA variants was 65% (31 patients) and two patients had two concomitant variants (E542Q-H1047R and R93W-E542A). In HGSC (55 pts), we found a BRCA1 variant in 36% of pts (median VAF: 80%) and a BRCA2 variant in 5% of pts. In high-grade endometrioid carcinoma (19 pts), a PIK3CA variant was found in 18% of patients, PTEN in 11% and POLE in 5%. Including low-level gains, ERBB2 was amplified in 6 patients (13%). ERBB2 and MET had a high-level amplification (5 copies) in 1 patient each. Three patients had a fusion: 1 FGFR1, 1 FGFR2 and 1 ROS1.ConclusionsThe increasing approval of targeted therapies in early stages neoplasms such as lung cancer, prompted us to investigate the prevalence and nature of actionable mutations in EOC, postulating the potential introduction of chemotherapy-free regimens or targeted maintenance therapy in this context.Clinical trial identificationNCT06020625.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureC. Nero: Financial Interests, Personal, Other, Travel Support: MSD, Illumina. A. Fagotti: Financial Interests, Personal, Advisory Board, Advisory Board AstraZeneca: AstraZeneca & MSD; Financial Interests, Personal, Invited Speaker, Speaker: PharmaMar, Johnson & Johnson, Fondazione Internazionale Menarini; Financial Interests, Personal, Invited Speaker, Moderator: GSK; Financial Interests, Institutional, Coordinating PI, NUVOLA trial-NCT04261465: AstraZeneca; Financial Interests, Institutional, Coordinating PI, ENSEAL® X1 Curved Jaw Tissue Sealer: Johnson & Johnson; Financial Interests, Institutional, Coordinating PI, PROTOCOL ID: Microvesicles INnovative OvaRian CAncer (MINORCA). ID2368Studio osservazionale valutante gli esosomi e le microvescicole circolanti con tecnologie innovative in qualità di potenziali biomarcatori per personalizzare il trattamento del carcinoma sieroso di alto grado ovarico: Roche. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca & MSD, Olympus Europa, GSK, AstraZeneca & MSD, Olympus Europa; Financial Interests, Personal, Advisory Board, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Coordinating PI, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Coordinating PI, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Coordinating PI, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Coordinating PI, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Coordinating PI, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Coordinating PI, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. All other authors have declared no conflicts of interest.