Abstract B005: Impact of molecular profiling and ESCAT classification on patient outcome: The experience of Institut Curie Molecular Tumor Board

Abstract

Abstract Introduction: The European Society of Medical Oncology Scale of Actionability of molecular Targets (ESCAT) classification system provides a standardized framework for categorizing genomic alterations (GA) of advanced cancer patients. We aimed to analyze the impact of matched therapies administered based on GAs identified through Institut Curie Molecular Tumor Board (MTB) between January 2018 and December 2022, according to ESCAT classification. Patients and methods: Between 2018 and 2022, 1,445 patients were discussed at Institut Curie MTB. Inclusion criteria were pre-defined as: adult patients (>18 years) with advanced or rare cancers. Tumors characteristics, pathological and genomic analyses, MTB conclusions, and follow-up after MTB were collected. Molecular analyses included a custom in-house NGS panel of 571 genes (DRAGON) and targeted RNAseq (ARCHER FusionPlex® CTL panel) or WGS, WES and RNAseq performed on the SEQOIA platform as part of the French Genomic Medecine Plan 2025. Clinical endpoints were Objective Response Rates (ORR), Progression-Free Survival (PFS) and Overall Survival (OS). ORR, PFS and OS of the population of patients receiving matched therapies were analyzed according to ESCAT Tiers. Results: Median patients age was 59 in the global MTB population (range=18-95; n=1,445) and mostly females (968/1,445; 67%). Most frequent tumors were from breast (20%), head and neck (10%), pancreas (10%), colon/rectum (9%), ovary (7%), lung (7%), soft tissue (7%), uterus (6%) or uveal melanoma (5%). Of the 1,445 patients, 995 had a tumor molecular profiling (69%). Actionable GAs were found in 576/995 (58%) of patients and 211/995 (21%) patients were oriented towards matched therapy. Simultaneously, some patients have also been referred to a genetic consultation when GA may correspond to a known predisposition gene. Among the 211 patients oriented towards matched therapy and after clinical evaluation for each patient, 101/211 (47%) representing 101/995 (10%) of the total patients actually received a matched therapy according to 102 actionable GAs identified through MTB analysis. The main actionable GAs detected were found in PIK3CA (12%), ERBB2 (11%), BRCA2 (6%) and FGFR3 (5%) genes. Among these, 40/102 GAs (40%) were classified as tier I, 4 (4%) as tier II, 35 (35%) as tier III, 18 (18%) as tier IV and 5 (5%) as tier X according to ESCAT. For those patients, PFS and OS were significantly improved when treatment was administered based on ESCAT tiers I/II (p=0.0486 for PFS, and p=0.0224 for OS). Worst clinical outcomes were observed for hypothetical targets classified as Tiers III and IV. Conclusions: High throughput screening was feasible for a majority of patients enrolled in the MTB. Among the patients screened, actionable GAs are identified in 58% of the patients. Yet 21% were oriented to matched therapy. Finally, 10% of patients were eventually treated with matched therapy, with a favorable outcome observed in patients with ESCAT Tiers I/II. Citation Format: Maud Kamal, Kimya Rahmani Narj Abadi, Raphaël Sanchez, Célia Dupain, Isabelle Guillou, Grégoire Marret, Zahra Castel Ajgal, Marie Paule Sablin, Cindy Neuzillet, Amani Asnacios Lecerf, Edith Borcoman, Ségolène Hescot, Florence Coussy, Manuel Rodrigues, Nicolas Girard, Sarah Watson, Julien Masliah Planchon, Jennifer Wong, Abderaouf Hamza, Celine Callens, Olfa Trabelsi Grati, Samia Melaabi, Keltouma Driouch, Emmanuelle Mouret-Fourme, Chrystelle Colas, Samantha Antonio, Odette Mariani, Michèle Nijnikoff, Anne Vincent-Salomon, Yves Allory, Ivan Bieche, Christophe Le Tourneau. Impact of molecular profiling and ESCAT classification on patient outcome: The experience of Institut Curie Molecular Tumor Board [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B005.