Background: Lenvatinib inhibits VEGFR, FGFR, PDGFRα. These targets have been shown to be expressed in patients with biliary tract cancer (BTC). A planned interim analysis of this phase 2 study demonstrated preliminary efficacy of lenvatinib 24 mg/d in patients with BTC.
Methods: This open-label phase 2 study conducted in Japan enrolled patients aged ≥20 years with confirmed unresectable BTC, measurable disease per RECIST v1.1, and 1 prior gemcitabine-based doublet chemotherapy to receive lenvatinib 24 mg/d. The primary endpoint was objective response rate (ORR). Secondary objectives included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), safety, and pharmacokinetics.
Results: The primary analysis was performed with data on 26 patients. Median age was 64 years and 15 patients (58%) were men. ECOG PS was 0 for 19 patients (73%) and 1 for 7 patients (27%). Six patients (23%) had prior surgery, 20 (77%) received prior GEM + cisplatin therapy, and 6 (23%) received prior gemcitibine+TS-1. Six patients (23%) had intrahepatic bile duct, 8 (31%) extrahepatic bile duct, 10 (39%) gallbladder, and 2 (8%) ampulla of Vater primary tumor locations. ORR was 12% (90% CI: 3.2‒27.2) by both independent and investigator review. DCR was 85% (90% CI, 68.2‒94.6) by investigator, and 46% (90% CI, 29.2‒63.8) by independent review. Median PFS was 3.2 months (95% CI, 2.8‒7.2) and 1.6 months (95% CI, 1.4‒3.2) by investigator and independent review, respectively. Median OS was 7.4 months (95% CI, 4.5‒11.3). All patients had TEAEs. Common TEAEs included hypertension, dysphonia, proteinuria, palmar-plantar erythrodysesthesia, decreased appetite, thrombocytopenia, and fatigue. TEAEs led to dose reduction in 20 patients (77%) and discontinuation in 2 (8%).
Conclusions: Lenvatinib 24 mg/d showed anti-tumor activity in patients with unresectable BTC who had failed gemcitabine-based combination therapy. Toxicities were manageable with dose modifications, reductions, or discontinuations.