190P EORTC-SPECTA Arcagen project: Results of the prospective rare thoracic tumors cohort

Rare cancers are usually under-represented in clinical research including genomic profiling. Arcagen is a European study aiming at defining the molecular landscape of rare cancers for treatment guiding. We present data from the prospective cohort of rare thoracic tumors. Patients with malignant pleural mesothelioma (MPM) or thymic tumors (TT) at advanced stage underwent genomic profiling by FoundationOne CDx on FFPE blocks, or alternatively by FoundationOne Liquid CDx on newly collected plasma samples. Molecular tumor boards (MTB) discussed patients’ molecular and clinical profile to advise for possible biomarker-guided treatments, including clinical trial options. Overall, 102 patients recruited from 8 different countries between July 2019–May 2022 were evaluable: 56 patients with MPM, 46 with TT (23 thymomas, 23 thymic carcinomas). One third were female (21% for MPM, 54% for TT), the median age at diagnosis was 70 (IQR 55–74), 29% of the patients were first managed with a curative intent (9% MPM, 54% TT). Molecular profiling was performed on 70 FFPE samples (42 MPM, 28 TT), while in 32 cases the analysis was done on cfDNA (14 MPM, 18 TT), within a median turnaround time of 8 days. We detected relevant molecular alterations in 64 out of 102 patients (63%; 77% MPM, 46% TT), specifically in 49 of 70 FFPE samples (70%; 88% MPM and 32% TT) and 15 of 32 plasma samples (47%; 43% MPM and 50% TT). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in MPM, while TP53, CDKN2A/B, SETD2 in TT. The tumor mutational burden was low across all tumor types (mean 3.2 Muts/MB), 2 tumors had MSI-high status. MTB advised for potential treatment options in 39 situations (including non-biomarker driven trials in 8 cases), for 17 MPM and 22 TT patients, and gave indication to genetic or hematologic counseling for 7 patients (mostly due to the detection of germline pathogenic variants in BAP1 or clonal hematopoiesis). We found relevant genomic alterations in 63% of rare thoracic tumors, allowing broadening the treatment options for at least 30% of the patients according to MTB recommendation. cfDNA analysis efficiently recovered cases that had inadequate tumor material. Molecular testing and drug accessibility should be implemented for these patients.