Synergistic toxicity and clinical prioritization of docetaxel combined with nintedanib for non-small cell lung cancer: a real-world safety analysis using the FAERS database.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 85% of new lung cancer diagnoses. Although docetaxel-nintedanib combination therapy improves survival in previously treated NSCLC, its real-world safety profile has not been comprehensively characterized. This study aimed to comprehensively characterize the real-world safety profile of docetaxel, nintedanib, and their combination in patients with NSCLC. METHODS: We retrieved adverse drug reaction(ADR) reports associated with docetaxel, nintedanib monotherapy and their combination in NSCLC patients from the FAERS database. Disproportionality analyses using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were performed, followed by clinical priority scoring and time-to-onset analyses. RESULTS: A total of 54, 66, and 78 significant PT-level safety signals were identified for docetaxel monotherapy, nintedanib monotherapy, and their combination therapy, respectively, and all signals remained significant after BH-FDR correction (P<0.05). Compared with either monotherapy, the combination regimen demonstrated a broader toxicity spectrum with relatively greater reporting of hematologic, gastrointestinal, infectious, and hepatobiliary adverse reactions. Combination therapy showed disproportionately strong signals for mucosal infection (ROR = 343.76, IC = 8.40, p<0.001), metastases to adrenals (ROR = 90.15, IC = 6.49, p<0.001) and portal vein thrombosis (ROR = 28.43, IC = 4.83, p<0.001). Docetaxel monotherapy was predominantly associated with skin and psychiatric disorders, whereas nintedanib monotherapy was predominantly associated with hepatic injury and thromboembolic events. Clinical prioritization identified febrile neutropenia, intestinal perforation, and sepsis as the highest-priority adverse events in the combination group. Median time-to-onset was shorter for combination therapy than for docetaxel or nintedanib monotherapy (22.5 vs. 34.5 and 34.5 days, Log-rank p<0.001). Weibull analysis indicated an early-failure pattern (β < 1) for all three regimens. CONCLUSION: This study provides a comprehensive real-world comparison of the safety profiles of docetaxel, nintedanib, and their combination, identifying distinct toxicity patterns and clinically important adverse reactions. These findings may facilitate individualized safety monitoring and optimize toxicity management in patients with NSCLC.