Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results

BackgroundBiliary tract cancer (BTC) has a poor prognosis and lacks a standardized second-line therapy. Vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR) 4, and platelet-derived growth factor receptor (PDGFR) are highly expressed in BTC. Therefore, lenvatinib (a known inhibitor of VEGF receptors 1-3, FGFRs 1-4, and PDGFR-alpha) was evaluated for second-line treatment of BTC.MethodsIn this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24mg orally once daily in 28-daycycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles.ResultsTwenty-six Japanese patients were enrolled and treated; 3 had a confirmed partial response per investigator assessment and per independent imaging review (IIR); ORR was 11.5% (90% confidence interval [CI]: 3.2-27.2). Median PFS was 3.19months (95% CI: 2.79-7.23) per investigator assessment and 1.64months (95% CI: 1.41-3.19) per IIR. Median OS was 7.35months (95% CI: 4.50-11.27). Grade >= 3 treatment-emergent adverse events (TEAEs) occurred in 21 patients (80.8%) and included hypertension (n=10 [38.5%]), proteinuria (n=3 [11.5%]), palmar-plantar erythrodysesthesia (n=3 [11.5%]), decreased appetite (n=3 [11.5%]), and anemia (n=3 [11.5%]). Two deaths occurred due to TEAEs between treatment initiation and 30days after last dose, but neither were considered treatment related.ConclusionsLenvatinib demonstrated antitumor activity in BTC, with a tolerable safety profile, and should be further evaluated as potential second-line therapy for this difficult to treat population.Trial registrationClinicalTrials.gov NCT02579616. Date of registration: October 19, 2015.