Dose modification and therapy interruption due to adverse events in treatment with anlotinib for refractory advanced NSCLC: Data from ALTER0303

Abstract

Background: Anlotinib is an oral tyrosine kinase inhibitor targeting VEGFR, FGFR, PDGFR and c‐kit. Anlotinib showed significantly improvement in overall survival in ALTER0303 trial for refractoryNSCLC, a randomized, double‐blind, placebo‐controlled phase III trial in China. This study reported the tolerance of anlotinib in the ALTER0303. Methods: The adverse events (AEs), dose modification, and therapy interruption were collected from anlotinib group (n=294) and placebo group (n=143) that were enrolled in ALTER0303. AEs were graded using Common Terminology Criteria. Results: The anlotinb related grade ≥3 AEs reported in≥1% patients were hypertension (13.3%), hyponatremia (4.8%), hand‐foot syndrome (HFS) (3.7%), hemoptysis (3.1%), GGT elevation (2.7%), hypertriglyceridemia (2.4%), QT interval prolongation (2.4%), lipase elevation (2.4%), proteinuria (2.4%), oral mucositis (1.0%), diarrhea (1.0%), and hyperbilirubinemia (1.0%). Grade≥3 hypertension, HFS, and hypertriglyceridemia were significantly more frequent in the anlotinib group than in the control group. Dose reduction and drug interruption were required in 24 (8.16%) (Table) and 31 (10.54%) patients in anlotinib group, respectively. The most common anlotinibrelated AEs causing interruption were hemoptysis (2.3%), venous thromboembolism (1.0%), proteinuria (0.7%), interstitial lung disease (0.7%), and pneumothorax (0.7%). (Table Presented) Conclusions: It was important to manage hand‐foot syndrome, hypertension, diarrhea and hemoptysis, so that patients could benefit from anlotinib.