{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(4)"],"submitter":["Gulikers JL"],"pubmed_abstract":["<h4>Introduction</h4>Brain metastases (BM) are common in patients with advanced <i>EGFR</i>-mutated (<i>EGFR</i>m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C<sub>min,SS</sub>) and consequently limited intracranial osimertinib exposure. We investigated the relation between osimertinib C<sub>min,SS</sub> and BM development or progression.<h4>Methods</h4>A prospective multicenter cohort study, including patients receiving osimertinib for advanced <i>EGFR</i>m<i>+</i> NSCLC. At osimertinib start, patients were allocated to the BM or no or unknown BM cohort and were further divided into subgroups based on osimertinib C<sub>min,SS</sub> (low, middle, and high exposure). Cumulative incidence of BM progression or development and overall survival were determined for each group.<h4>Results</h4>A total of 173 patients were included, with 49 (28.3%) had baseline BM. Of these patients, 36.7% experienced BM progression, of which 16.7% in the low (<159.3 ng/mL), 40.0% in the middle, and 47.1% in the high (>270.7 ng/mL) C<sub>min,SS</sub> subgroups. After 12 months, the cumulative incidence of BM progression for the BM cohort was 20% (95% confidence interval [CI] 2.6-49.0), 31% (95% CI:10.6-53.9), and 31% (95% CI:10.8-54.5) per C<sub>min,SS</sub> subgroup, respectively. After 20 months, this was 20% (95% CI:2.6-49.0), 52% (95% CI:23.8-74.2), and 57% (95% CI:24.9-79.7), respectively. For the no or unknown BM cohort, 4.0% developed BM without differences within C<sub>min,SS</sub> subgroups.<h4>Conclusions</h4>No relation was found between osimertinib C<sub>min,SS</sub> and BM development or progression in patients with advanced <i>EGFR</i>m<i>+</i> NSCLC. This suggests that systemic osimertinib exposure is not a surrogate marker for BM development or progression."],"journal":["JTO clinical and research reports"],"pagination":["100656"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10973185"],"repository":["biostudies-literature"],"pubmed_title":["Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced <i>EGFR</i>-Mutated NSCLC."],"pmcid":["PMC10973185"],"pubmed_authors":["Kruithof PD","Dursun S","Mathijssen RHJ","Tjan-Heijnen VCG","Jebbink M","Hendriks LEL","Veerman GDM","Driessen JHM","Croes S","Dingemans AC","Steendam CMJ","Gulikers JL","Boosman RJ","Smit EF","van Geel RMJM"],"additional_accession":[]},"is_claimable":false,"name":"Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced <i>EGFR</i>-Mutated NSCLC.","description":"<h4>Introduction</h4>Brain metastases (BM) are common in patients with advanced <i>EGFR</i>-mutated (<i>EGFR</i>m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C<sub>min,SS</sub>) and consequently limited intracranial osimertinib exposure. We investigated the relation between osimertinib C<sub>min,SS</sub> and BM development or progression.<h4>Methods</h4>A prospective multicenter cohort study, including patients receiving osimertinib for advanced <i>EGFR</i>m<i>+</i> NSCLC. At osimertinib start, patients were allocated to the BM or no or unknown BM cohort and were further divided into subgroups based on osimertinib C<sub>min,SS</sub> (low, middle, and high exposure). Cumulative incidence of BM progression or development and overall survival were determined for each group.<h4>Results</h4>A total of 173 patients were included, with 49 (28.3%) had baseline BM. Of these patients, 36.7% experienced BM progression, of which 16.7% in the low (<159.3 ng/mL), 40.0% in the middle, and 47.1% in the high (>270.7 ng/mL) C<sub>min,SS</sub> subgroups. After 12 months, the cumulative incidence of BM progression for the BM cohort was 20% (95% confidence interval [CI] 2.6-49.0), 31% (95% CI:10.6-53.9), and 31% (95% CI:10.8-54.5) per C<sub>min,SS</sub> subgroup, respectively. After 20 months, this was 20% (95% CI:2.6-49.0), 52% (95% CI:23.8-74.2), and 57% (95% CI:24.9-79.7), respectively. For the no or unknown BM cohort, 4.0% developed BM without differences within C<sub>min,SS</sub> subgroups.<h4>Conclusions</h4>No relation was found between osimertinib C<sub>min,SS</sub> and BM development or progression in patients with advanced <i>EGFR</i>m<i>+</i> NSCLC. This suggests that systemic osimertinib exposure is not a surrogate marker for BM development or progression.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2025-04-26T11:21:26.895Z","creation":"2025-04-06T13:41:05.683Z"},"accession":"S-EPMC10973185","cross_references":{"pubmed":["38550297"],"doi":["10.1016/j.jtocrr.2024.100656"]}}