Actionable non-small cell lung cancer mutation identification by comprehensive genomic profiling for clinical trial enrollment: the European Program for the ROutine testing of Patients with Advanced lung cancer (EPROPA)

To reduce the gap about the relevant heterogeneity of molecular testing and cancer care across Europe, Women Against Lung Cancer in Europe (WALCE) promoted the European Program for ROutine testing of Patients with Advanced lung cancer (EPROPA) and provided a free-of-charge molecular profiling platform for non-small cell lung cancer sample characterization with the aim of increasing the detection of targetable drivers and improving patients' access to clinical trials. From January 2021 to December 2023, 20 centres located at 5 different European countries (Greece, Slovenia, Romania, Albania and Italy) joined EPROPA, with 555 advanced NSCLC patients registered into the program. Anonymized patients' clinical-pathological data were shared through the EPROPA web platform and tissue samples were collected to the Molecular Pathology Unit of the Reference Center (University of Turin) for molecular analyses. A comprehensive genomic profiling by targeted next-generation sequencing approach has been performed and molecular reports have been discussed within the molecular tumour board (MTB) in order to assess patients' eligibility for clinical trials. The average turnaround time was 8 days, with only 30 out of 555 (6%) tissue samples not suitable for molecular analysis. Among the 525 analyzed samples, a total of 570 molecular alterations have been identified, including 264 pathogenic targetable oncogenic alterations and 113 cases with co-occurring mutations. A total of 18 molecular alterations with potential germline and hereditary cancer syndrome implications have been reported. The identification of a clinical trial was considered for 205 patients. After MTB discussion, 30 patients were enrolled and treated in clinical studies available in Europe. Survival outcome were significantly improved in patients with targetable molecular alterations receiving a matched targeted therapy. This data confirmed the feasibility and usefulness of the program in the real-world practice scenario, supporting the implementation of NGS-based molecular characterization of NSCLC samples, in order to reduce the unequal access to tests, drugs and clinical trials in Europe.