Abstract Introduction Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for patients with advanced non-small cell lung cancer (NSCLC). First- and second-generation TKIs, (e.g., Erlotinib, Afatinib), offer clinical benefit but are often limited by adverse events (AEs) and resistance. Osimertinib, a third-generation TKI, was developed to overcome these limitations with improved central nervous system (CNS) penetration and a more favorable toxicity profile. In our prior real-world data (RWD) study, Afatinib demonstrated lower infection risk but higher gastrointestinal and dermatologic toxicity compared to Erlotinib. Here, we extend this work by comparing the AE profile of Afatinib with Osimertinib using RWD. Methods We conducted retrospective cohort study using TriNetX database, a global federated health research network of electronic medical records. Patients with NSCLC treated with Afatinib (n = 2,446) or Osimertinib (n = 9,011) were identified based on a diagnosis of malignant neoplasm of the bronchus and lung and receipt of the respective drug between January 1, 2018, and October 1, 2024. Propensity score matching balanced baseline characteristics (age, race, sex, smoking status), yielding 2,811 patients per group. AEs were compared using risk ratios (RRs) and 95% confidence intervals (CIs). Results Afatinib was associated with higher risk of pneumonia (RR 1.28, CI 1.15-1.42, p 0.001), diarrhea (RR 1.31, CI 1.15-1.50, p 0.0001), paronychia (RR 2.25, CI 1.87-2.72, p 0.0001), pruritus (RR 1.59, CI 1.23-2.04, p 0.0001), vomiting (RR 1.40, CI 1.05-1.86, p = 0.021), and brain metastases (RR 1.26, CI 1.09-1.45, p = 0.001). Conversely, Afatinib showed lower risk of nausea (RR 0.72, CI 0.59-0.88, p = 0.001) and appetite loss (RR 0.76, CI 0.62-0.93, p = 0.007). Conclusions Compared to Afatinib, Osimertinib demonstrated a more favorable AE profile in a real-world setting, including lower rates of CNS progression. These findings support its use as a preferred TKI option in EGFR-mutated advanced NSCLC. This abstract is funded by: None
Atalayer et al. (Fri,) studied this question.