5P Ovarian cancer ESCAT gene actionability: Cinderella wears the gown

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. 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. 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%). 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.