Abstract 5P
Background
In recent years, the prognosis of several malignancies has been positively influenced by the introduction of target therapy. In this context, ovarian cancer (OC) has played a minor role and chemotherapy still represents the backbone of standard treatment both in first and in subsequent lines. In 2023, BRCA1-2 and Homologous recombination deficit (HRD) status were included as Tier IA in the European Society of Medical Oncology Scale for Clinical Actionability (ESCAT) for OC.
Methods
In January 2022 our institution launched a comprehensive cancer genome profiling (CGP) (FPG500 IRB approval 3837; NCT06020625) enrolling patients with several neoplasms including OC, 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 count the rate of ESCAT I-II-III actionable and potentially actionable alterations.
Results
From January 1st 2022 to December 31st 2023, 832 patients with OC (72% high grade serous ovarian cancer, 9% endometroid cancer, 7% clear cells histology and 12% other histologies) underwent CGP, 338 of whom were also characterized for HRD. Overall, 47% showed at least one actionable or potentially actionable genomic alteration according to the ESCAT classification (level I, II, III). Concerning level IA, 15% and 9% were BRCA1 and BRCA 2 mutated, respectively, 53% were HRD. FGFR2 mutations were 2% (Tier IC). The most frequently found level II-III ESCAT genomic alterations were: PIK3CA mutations (13%), PTEN (mutations 4,7%, homdel 2,3%), ATM mutations (3%) and ERBB2 mutations (2%).
Conclusions
In the era of chemo free treatment, a wide genomic profiling in OC could pave the way to potential targeted approaches expanding therapeutic opportunities especially for BRCA 1/2 WT and HR proficient population.
Clinical trial identification
NCT06020625.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Nero: Financial Interests, Personal, Other, Travel support: Illumina, MSD. 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, Invited Speaker, NUVOLA trial-NCT04261465: AstraZeneca; Financial Interests, Institutional, Invited Speaker, ENSEAL® X1 Curved Jaw Tissue Sealer: Johnson & Johnson; Financial Interests, Institutional, Invited Speaker, 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. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Personal, Member, Board of Directors: GCIG; Other, Personal, Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. 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, Expert Testimony, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Invited Speaker, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Invited Speaker, 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, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, 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, Invited Speaker, 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, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Invited Speaker, 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.