Efficacy and Safety of Lucitanib in Advanced Thymic Carcinoma: A Randomized Phase II Trial

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.