A recent study published in Scientific Reports has identified a potential biomarker for predicting adverse drug reactions (ADRs) in patients with advanced non-small cell lung cancer (NSCLC) treated with Osimertinib. The research indicates that the length of telomeres in blood leukocytes is significantly shorter in patients who experience severe ADRs from Osimertinib, suggesting its utility in identifying high-risk individuals.
The study, which included 63 patients with advanced-stage NSCLC and 62 healthy controls, found that patients with NSCLC had significantly shorter blood leukocyte telomere length compared to healthy individuals [3.94 (1.52, 8.79) vs. 10.07 (6.74, 17.60), P < 0.0001]. Furthermore, among NSCLC patients, those who experienced severe ADRs from Osimertinib had markedly shorter telomere length compared to those with mild/moderate ADRs [1.52 (1.12, 2.91) vs. 5.55 (4.14, 9.96), P < 0.0001].
Osimertinib and Adverse Reactions
Osimertinib is a targeted therapy commonly used in NSCLC patients with EGFR mutations. While effective, it is associated with various ADRs, including skin issues, gastrointestinal problems, and QTc prolongation. The study categorized ADRs into mild/moderate and severe, with the most common ADRs being skin-related (acne, dry skin) and digestive (diarrhea).
Telomere Length as a Biomarker
Telomeres are protective caps on the ends of chromosomes, and their length tends to shorten with age and cellular stress. The study found a strong negative correlation between blood leukocyte telomere length and the severity of Osimertinib-induced ADRs (r = -0.82, P < 0.0001). ROC curve analysis indicated that a blood leukocyte RTL cutoff value of 3.055 could differentiate between patients with severe versus mild/moderate ADRs, with a sensitivity of 100.0% and a specificity of 80.0% (AUC = 0.932, 95% CI 0.86–1.00; P < 0.0001).
Clinical Implications
These findings suggest that measuring telomere length in blood leukocytes could help identify NSCLC patients at higher risk of developing severe ADRs from Osimertinib. This could potentially allow for personalized treatment strategies, such as dose adjustments or closer monitoring, to mitigate the impact of ADRs and improve patient outcomes. While shorter telomere length was associated with a higher cumulative incidence of ADRs overall (log-rank: Chi-square = 12.33, P < 0.001), the association with severe ADRs specifically did not reach statistical significance (log-rank: Chi-square = 3.44, P = 0.064). Further research with larger cohorts is warranted to validate these findings and explore the underlying mechanisms linking telomere length and drug sensitivity.
