151P Molecular epidemiology and real-world outcomes of genomically-matched non-squamous non-small cell lung cancer (nsNSCLC) patients in a diverse Brazilian population

R. Dienstmann, T. Montella, F. Orpinelli,R.D. Paes, P.R. De Marchi, F.C. Koyama,C.B. Fernandes, L.T. Galindo, B.B. de Souza, F.A. Duarte, F.L.V. Visani,I.S. Negreiros, N. Afonso, P.N. Aguiar, T. Vilasboas Reis, C.M. De Cerqueira Mathias,L.M. Da Silva, C. Leslin, M.G. Zalis,C.G.M. Ferreira

Journal of Thoracic Oncology(2023)

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摘要
The prevalence of actionable drivers in nsNSCLC may vary according to ancestry and performance of the next-generation sequencing (NGS) assay. In Brazil, comprehensive genomic profiling of nsNSCLC is sponsored by pharma support programs with tests performed in-house (Oncoclínicas Precision Medicine – OCPM) or abroad. We aimed to assess prevalence of actionable drivers in a real-world clinico-genomics cohort with linked survival outcomes under genomically-matched therapies. All patients prospectively recruited in the OCPM Lung Mapping consortium from January 2020 to December 2022 were assessed for driver prevalence. Archived formalin-fixed paraffin-embedded (FFPE) tumor material underwent sequencing with GS180 panel (Archer Dx DNA/RNA assay). We calculated median overall survival (mOS) of nsNSCLC patients that received targeted therapies at Oncoclínicas during the same period with Kaplan-Meier method (from diagnosis date of metastatic disease until the last follow-up or death). In total, 592 patients had informative GS180 results for driver mutations and/or fusions, with 313 cases (52.9%) harboring actionable alterations: EGFR mutations in 25.5% (exon 20 insertion in 3.5%), KRAS G12C in 7.9%, MET exon 14 skip in 5.4%, ALK fusion in 5.2%, ERBB2 mutations in 3.2%, ROS1 fusion in 2%, BRAF V600E in 1.5%. RET/ NTRK1-3/NRG1 fusions in <1%. We identified 373 patients with exposure to genomically matched targeted agents at Oncoclínicas when considering all metastatic nsNSCLC population, irrespective of the laboratory used for molecular diagnosis. With median follow-up of 13 months, 62% received targeted therapy in first-line, and mOS was 30.6 months (95% CI, 26–43). Molecular epidemiology of nsNSCLC in Brazilian patients is unique when compared to published literature in European and North American cohorts, with numerically higher prevalence of EGFR mutations, MET exon 14 skip and ALK fusions. These results may be in part explained by fusion sensitivity with RNA sequencing. Survival outcomes for those treated with targeted agents are promising, but a large proportion of the patients still receive non-matched therapies in the first-line.
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lung cancer,molecular epidemiology,brazilian population,real-world,genomically-matched,non-squamous,non-small
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