Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis
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RESEARCH ARTICLE
Open Access
Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results Makoto Ueno1†, Masafumi Ikeda2*† , Takashi Sasaki3, Fumio Nagashima4, Nobumasa Mizuno5, Satoshi Shimizu6, Hiroki Ikezawa7, Nozomi Hayata7, Ryo Nakajima8 and Chigusa Morizane9
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. Keywords: Lenvatinib, Biliary tract cancer, Cholangiocarcinoma, Gallbladder cancer, Ampulla of Vater
* Correspondence: [email protected] † Makoto Ueno and Masafumi Ikeda contributed equally to this work. 2 Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other thir
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