Early loss of skeletal muscle index was not associated with osimertinib trough concentrations but was an independent predictor of shorter overall survival in patients with advanced EGFR-mutated NSCLC.
More than half of patients experienced skeletal muscle index loss during the first three months of osimertinib therapy.
There was no statistically significant association between skeletal muscle index loss and osimertinib trough concentrations over time.
Skeletal muscle index loss was not associated with progression-free survival.
Early loss of skeletal muscle index was an independent predictor of shorter overall survival after adjusting for confounders.
Patients in the highest-quartile osimertinib trough concentration and those with EGFR exon 21 L858R mutations had shorter progression-free survival.
The study design used linear mixed-effects modeling and Cox proportional hazards models to evaluate body composition and treatment outcomes.
This research examined whether patients with advanced lung cancer (specifically EGFR-mutated non-small cell lung cancer) who lost muscle mass during the first three months of treatment with osimertinib — a targeted therapy — had different drug levels in their blood or different treatment outcomes. The study included 53 patients and found that over half (56%) lost a meaningful amount of skeletal muscle within the first three months of starting treatment. However, the amount of drug circulating in a patient's bloodstream did not appear to be related to whether they lost muscle, suggesting that drug exposure alone is not what drives early muscle wasting in these patients. Despite muscle loss not being linked to how long patients lived without their cancer progressing, it was significantly associated with shorter overall survival. Patients who lost muscle in the first three months survived a median of about 25.5 months compared to nearly 30 months for those who did not lose muscle, and this difference held up even after accounting for drug levels and the presence of a TP53 gene mutation. Additionally, patients with higher drug concentrations and those with a specific type of EGFR mutation (exon 21 L858R) also tended to have shorter progression-free survival. This research suggests that early muscle loss during osimertinib treatment is a meaningful warning sign for poorer long-term outcomes, independent of how much drug is in the patient's system. The authors propose that future studies should investigate whether nutritional interventions or other strategies to preserve muscle mass during treatment might improve survival outcomes for these patients.
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Upload Your LabsSikkema B, Veerman M, Hoop E, Paats M, Mathijssen R, Dingemans A. (2026). Associations between early loss of skeletal muscle and osimertinib trough concentrations in patients with advanced EGFR-mutated NSCLC.. European journal of cancer (Oxford, England : 1990). https://doi.org/10.1016/j.ejca.2026.116742