Efficacy and Safety of Lucitanib in Advanced Thymic Carcinoma: A Randomized Phase II Trial
Wentao Fang, Caicun Zhou, Changlu Wang, Kailiang Wu, Jianhua Fu, Xiaoyan Lin, Helong Zhang, Jianhua Chen, Peng Zhang, Yiping Zhang, Peng Tang, Yulong Zheng, Yanping Liu, Xiuyi Zhi, Zhancheng Gao, Qingxia Fan, Huiming Cai, Fugen Li, Xiaoning Guo, Bo Zhang, Rongji Mu, Zhangsheng YuABSTRACT
Advanced thymic carcinoma is a rare, aggressive malignancy with limited treatment options after chemotherapy failure. This randomized, double‐blind, placebo‐controlled trial (AL3810‐202) aimed to evaluate lucitanib, a novel, orally potent tyrosine kinase inhibitor targeting VEGFR1‒3, FGFR1‒3, and PDGFRα/β in patients with advanced thymic carcinoma progressing after chemotherapy. Sixty‐eight patients were randomized (2:1) to receive 10 mg lucitanib daily ( n = 46) or placebo ( n = 22). Although this study did not meet its primary endpoint of independent review committee (IRC)‐assessed progression‐free survival (PFS) (median 5.8 vs. 3.7 months; hazard ratio [HR]: 0.60; p = 0.1050), the prespecified log‐rank test may have underestimated the treatment effect due to an observed non‐proportional hazards pattern. Subsequent restricted mean survival time analysis demonstrated a statistically significant PFS benefit ( p < 0.05), which was further supported by significantly prolonged investigator‐assessed PFS (6.6 vs. 1.9 months; HR: 0.53; p = 0.0306). The most common grade 3 treatment‐related adverse events (TRAEs) were hypertension (50%), proteinuria (15.2%), and thrombocytopenia (8.7%), with no grade 4/5 events. Considering the totality of the evidence and an acceptable safety profile, lucitanib may confer a meaningful clinical benefit for patients with advanced thymic carcinoma, warranting further investigation.