Lenvatinib (LEN) inhibits vascular endothelial growth factor receptors, fibroblast growth factor receptors, and platelet-derived growth factor receptor-α. These targets have been shown to be expressed in patients (pts) with biliary tract cancer (BTC). A planned interim analysis of this phase 2 study demonstrated preliminary efficacy of LEN 24 mg/d in pts with BTC.
This open-label phase 2 study conducted in Japan enrolled pts aged ≥ 20 years with a confirmed unresectable BTC, measurable disease per Response Evaluation Criteria in Solid Tumors v1.1, and 1 prior gemcitabine (GEM)-based doublet chemotherapy to receive LEN 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.
The primary analysis was performed with data on 26 pts. Median age was 64 years and 15 pts (58%) were men. Eastern Cooperative Oncology Group performance status was 0 for 19 pts (73%) and 1 for 7 pts (27%). Six pts (23%) had prior surgery, 20 pts (77%) received prior GEM + cisplatin therapy, and 6 pts (23%) received prior GEM + TS-1. There were 6 pts (23%) with intrahepatic bile duct, 8 (31%) with extrahepatic bile duct, 10 (39%) with gallbladder, and 2 (8%) with 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 pts had treatment-emergent adverse events (TEAEs). Common TEAEs included hypertension, dysphonia, proteinuria, palmar-plantar erythrodysesthesia, decreased appetite, thrombocytopenia, and fatigue. TEAEs led to dose reduction in 20 pts (77%) and discontinuation in 2 pts (8%).
LEN 24 mg/d showed anti-tumor activity in pts with unresectable BTC who had failed GEM-based combination therapy. Toxicities were manageable with dose modifications, reductions, or discontinuations.
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M. Ikeda: Honoraria: Novartis, Bayer Yakuhin, BMS, Abbott Jpn, Eisai, Taiho, Ono, Kowa, Eli Lilly Jpn, Chugai, Nippon Kayaku, Daiichi-Sankyo, Yakult; Research: Bayer Yakuhin, Kyowa Hakko Kirin, Yakult, Taiho, Eli Lilly Jpn, Boehringer, Ono, Eisai, AZ. C. Morizane: Honoraria: Pfizer, Novartis, Yakult Honsha, Eli, Nobelpharma, FUJIFILM RI Pharm.; Consulting/advisory: AstraZeneca, Yakult Honsha, Novartis, Taiho Pharm.; Research funding: GSK, Pfizer, Nobelpharma, Eisai, Yakult Honsha, ONO Pharm, Taiho Pharm. N. Mizuno: Research funding: Zeria Pharmaceutical, Taiho Pharmaceutical, Merck Serono, AstraZeneca, NanoCarrier, Eisai, and MSD Honoraria: Taiho Pharmaceutical, Yakult Honsha, Novartis, Pfizer, and Kyowa-Hakko Kirin Speaker\'s bureau: Taiho Pharmaceutical. F. Nagashima: Honoraria: Sanofi, Chugai, Mitsubishi Tanabe, Taiho, Nestle; Research funding: Taiho, Daiichi-Sankyo, Sanofi, Eli Lilly, Sumitomo Dainippon, Eisai, MSD. S. Shimizu: Honoraria: TAIHO, Nippon Kayaku, Novartis. N. Hayata, H. Ikezawa, T. Suzuki: Employment: Eisai Co., Ltd. R. Nakajima: Stock or other ownership: Astellas Pharma, Chion Bioscience. C. Dutcus: Employment: Eisai Inc. M. Ueno: Research funding: ONO Pharma, Baxalta. All other authors have declared no conflicts of interest.