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• W4286294369 abstract "4124 Background: Despite the frequent use of capecitabine and temozolomide (CAPTEM) to treat metastatic, well-differentiated pancreatic neuroendocrine tumors (PNETs), no reliable genomic predictors of response currently exist. PNETs commonly harbor mutations in MEN1, ATRX, DAXX, and the PI3K/AKT/mTOR pathway. We sought to determine whether the mutational status of these genes correlates with response to CAPTEM. Methods: A retrospective cohort of PNET cases seen at Cedars-Sinai Medical Center or from Perthera’s Real-World Evidence Database included 23 patients who were treated with CAPTEM in 1 st or 2 nd line and had targeted next-generation sequencing (NGS) of their tumors available. Genomic alterations were correlated with progression-free survival (PFS) using multivariate Cox regression analysis. Results: We analyzed 23 PNET patients, 4 (17.4%) of whom had documented functional tumors. We identified MEN1 mutations as positively associated with CAPTEM response, but this effect was less pronounced for the subset with co-occurring DAXX mutations, which are commonly found alongside MEN1 alterations. With and without accounting for line of therapy, we found that PFS on CAPTEM was significantly longer in MEN1-mutated, DAXX-wildtype tumors compared to other mutation profiles ( P < 0.01, see Table). ATRX (67%) and PTEN (33%) alterations were also enriched in the MEN1-mutated/ DAXX-wildtype subset; however, other PI3K/AKT/mTOR alterations were common across all MEN1-mutated cases. Conclusions: We describe a novel genomic signature ( MEN1 mut/ DAXX wt) that correlates with PNET response to CAPTEM therapy and is exploratory in nature. Prospective validation of these associations is warranted while taking into account other therapies, histopathologic factors, and other genomic correlates. [Table: see text]" @default.
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• W4286294369 date "2022-06-01" @default.
• W4286294369 modified "2023-09-26" @default.
• W4286294369 title "Genomic correlates of response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine tumors." @default.
• W4286294369 doi "https://doi.org/10.1200/jco.2022.40.16_suppl.4124" @default.
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