Molecular profiling and personalized medicine within EURACAN in the SPECTA Arcagen study in comparison to the France Genomic Medicine 2025 Plan in the AURAGEN platform in peritoneal mesotheliomas

Peritoneal mesothelioma (PM) is a rare aggressive cancer with limited therapeutic options upon progression. Two genomic profiling initiatives were launched to implement personalized medicine in rare cancers: the EURACAN molecular profiling and personalized medicine pathway and the France Genomic Medicine 2025 plan (AURAGEN). The aim of this study was to describe initial findings in PM and to compare these approaches in a real-world implementation setting. Herein, we present the results from a cohort of 56 patients with PM. Females represented 55.4% of patients; mean age was 55.9 years. The European (Arcagen) study profiled 26 patients and the AURAGEN platform profiled 42 patients. Genomic sequencing was performed using Foundation Medicine for the Arcagen cohort and whole-genome sequencing (WGS) for the AURAGEN cohort. Arcagen used FFPE tissue or blood depending on material availability, whereas AURAGEN relied on fresh frozen tumor tissue with paired blood (and RNA sequencing when feasible). Both cohorts displayed a predominance of alterations in BAP1, NF2, and CDKN2A/B. One patient with an ALK::STRN fusion was treated with Alectinib. AURAGEN identified a larger number of altered genes overall, while the proportion of therapeutic targets was similar between approaches. In conclusion, comprehensive molecular profiling offers potential therapeutic strategies for PM patients. Panel-based profiling and pan-genomic WGS appear complementary in real-world practice, each with distinct strengths and limitations.