Associations of early adverse events with clinical outcomes in patients with NSCLC treated with EGFR tyrosine kinase inhibitors.

Abstract

e20551 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) constitute the primary treatment modality for EGFR-mutant non-small cell lung cancer (NSCLC). While efficacious, EGFR TKIs are associated with adverse events (AEs) like dermatologic toxicities, diarrhea, and stomatitis. This study examined the prognostic implications of these on-target AEs in NSCLC patients receiving EGFR TKI therapy. Methods: A retrospective cohort study was conducted, encompassing advanced NSCLC patients treated with first-line EGFR TKIs within two distinct healthcare delivery systems in Taiwan between June 2011 and December 2019. Patients were stratified by TKI type, and those who had received AE reliever medications within 180 days prior to EGFR TKI initiation were excluded. We examined correlations between AEs and key endpoints: time to next treatment (TTNT) and overall survival (OS). To minimize immortal time bias, a landmark analysis at 60 days post-treatment initiation was utilized. On-target AEs were identified based on the issuance of at least two prescriptions for AE management on different dates within this period. Multivariable Cox proportional hazards models were utilized to evaluate the association between AEs and clinical endpoints, and a random-effects meta-analysis was performed to combine findings from both institutions. Results: Our analysis included 1,605 patients on gefitinib, 848 on erlotinib, and 1,236 on afatinib. Despite potential variations in AE reporting due to prescribing behaviors, the incidence of AE within the first 60 days of treatment was highest for afatinib, particularly with diarrhea (76.7%) and stomatitis (14.9%), followed by erlotinib with notable skin reactions (49.4%). Gefitinib showed the lowest incidence rates across all examined AEs. Of note, afatinib-treated patients who experienced diarrhea within the initial 60 days demonstrated a statistically significant extension in OS (HR 0.75, 95% CI 0.60-0.92). No significant prognostic link was found for other AEs in afatinib users or any AEs among users of gefitinib and erlotinib. Sensitivity analyses, incorporating modified AE definitions, corroborated these outcomes. Conclusions: Identifying AEs via prescription records for symptom relief poses methodological challenges and introduces uncertainty. Nevertheless, the occurrence of diarrhea within the first 60 days of therapy emerged as a significant predictor of enhanced OS in EGFR-mutant NSCLC patients receiving afatinib. This finding suggests a potential prognostic implication. The correlation was not evident in patients treated with first-line gefitinib or erlotinib.