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A phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: Primary analysis results

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx369.106

1569-8041

Masafumi Ikeda, Takashi Sasaki, Chigusa Morizane, Nobumasa Mizuno, Fumio Nagashima, Satoshi Shimizu, Nozomi Hayata, Hiroki Ikezawa, Takuya Suzuki, R. Nakajima, Corina E. Dutcus, Makoto Ueno,

Pancreatic and Hepatic Oncology Research

Background: 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. Methods: 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. Results: 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%). Conclusions: 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. Clinical trial identification: NCT02579616 Legal entity responsible for the study: Eisai Inc Funding: Eisai Inc Disclosure: 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.