EORTC-SPECTA Arcagen study, comprehensive genomic profiling and treatment adaptation of rare thoracic cancers

Introduction: Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guiding. We present data from the cohort of rare thoracic tumors. Methods: Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. Results: 102 patients recruited from 8 countries between July 2019-May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET) and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised for molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off label drug or compassionate use, 3% early access program). Conclusions: Molecular testing and MTB discussion are feasible for patients with rare thoracic cancers and allowed broadening of treatment options for 30% of the cases.