A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy.

Autor:	Furuse J; Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan., Ikeda M; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan., Ueno M; Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan., Furukawa M; Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyusyu Cancer Center, Fukuoka, Fukuoka, Japan., Morizane C; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan., Takehara T; Department of Gastroenterology and Hepatology, Osaka University Hospital, Suita, Osaka, Japan., Nishina T; Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan., Todaka A; Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan., Okano N; Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Tokyo, Japan., Hara K; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan., Nakai Y; Department of Gastroenterology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan., Ohkawa K; Division of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan., Sasaki T; Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan., Sugimori K; Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan., Yokoyama N; Department of Gastroenterological Surgery, Niigata City General Hospital, Niigata, Niigata, Japan., Yamamoto K; Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Sep 13; Vol. 30 (18), pp. 3990-3995.
DOI:	10.1158/1078-0432.CCR-24-0461
Abstrakt:	Purpose: To evaluate the efficacy and safety of nanvuranlat [an L-type amino acid transporter 1 inhibitor] monotherapy as a later-line treatment in advanced, metastatic, and refractory biliary tract cancers. Patients and Methods: A multicenter, randomized, double-blind, placebo-controlled phase II study was conducted across fourteen leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of 5 consecutive days, followed by 9 days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and disease control rate. Subgroup analysis was performed in patients with high L-type amino acid transporter 1 expression and biliary tract cancer subtypes. Results: A total of 211 patients were screened, of which 105 eligible patients were randomized. Among these, 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared with placebo (HR, 0.56; 95% confidence interval, 0.34-0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Conclusions: Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory biliary tract cancer with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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