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

Abstract

Background Biliary 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-α) was evaluated for second-line treatment of BTC. Methods In this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24 mg orally once daily in 28-day cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12 weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles. Results Twenty-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 3.19 months (95% CI: 2.79–7.23) per investigator assessment and 1.64 months (95% CI: 1.41–3.19) per IIR. Median OS was 7.35 months (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 30 days after last dose, but neither were considered treatment related. Conclusions Lenvatinib 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 registration ClinicalTrials.gov NCT02579616. Date of registration: October 19, 2015.

Systemic Sequential Therapy of CisGem, Tislelizumab, and Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma Conversion Therapy

“…Furthermore, the TMB was very high. Secondly, based on a phase II clinical study, lenvatinib was confirmed to have a tolerable safety profile for second-line treatment of CCA ( 34 ). Moreover, the cytotoxic cell death activity of chemotherapy would trigger antigen release, enhancing immune stimulation and improving the activity of PD-1/PD-L1-blocking agents ( 35 ).…”

Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics

“…Besides, capecitabine showed comparable effects when used as adjuvant chemotherapy following surgery in patients with resected biliary tract cancer either under or over 60 years old [ 134 ]. The still scarce results of the response to lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer have shown antitumor activity with a tolerable safety profile, with similar adverse events in patients under and over 65 years [ 135 ].…”

Recent Advances in the Mechanism Research and Clinical Treatment of Anti-Angiogenesis in Biliary Tract Cancer

“…Finally, 26 patients were recruited into the study, and the results showed that the median PFS was 3.19 months (95% CI: 2.79-7.23) and the median OS was 7.35 months (95% CI: 4.50-11.27). Therefore, the study authors concluded that lenvatinib showed promising therapeutic effects in advanced biliary tract tumors with manageable side effects (107). Regorafenib is a multitarget inhibitor that targets VEGFR, PDGFR-b, KIT, RET and RAF-1.…”