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

被引：6

作者：

Furuse, Junji ^{[1
]}

Ikeda, Masafumi ^{[2
]}

Ueno, Makoto ^{[1
]}

Furukawa, Masayuki ^{[3
]}

Morizane, Chigusa ^{[4
]}

Takehara, Tetsuo ^{[5
]}

Nishina, Tomohiro ^{[6
]}

Todaka, Akiko ^{[7
]}

Okano, Naohiro ^{[8
]}

Hara, Kazuo ^{[9
]}

Nakai, Yousuke ^{[10
]}

Ohkawa, Kazuyoshi ^{[11
]}

Sasaki, Takashi ^{[12
]}

Sugimori, Kazuya ^{[13
]}

Yokoyama, Naoyuki ^{[14
]}

Yamamoto, Kouji ^{[15
]}

机构：

[1] Kanagawa Canc Ctr, Dept Gastroenterol, Yokohama, Kanagawa, Japan

[2] Natl Canc Ctr Hosp East, Dept Hepatobiliary & Pancreat Oncol, Kashiwa, Chiba, Japan

[3] Natl Hosp Org Kyusyu Canc Ctr, Dept Hepatobiliary Pancreatol, Fukuoka, Fukuoka, Japan

[4] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Chuo Ku, Tokyo, Japan

[5] Osaka Univ Hosp, Dept Gastroenterol & Hepatol, Suita, Osaka, Japan

[6] Natl Hosp Org Shikoku Canc Ctr, Dept Gastrointestinal Med Oncol, Matsuyama, Ehime, Japan

[7] Shizuoka Canc Ctr, Div Gastrointestinal Oncol, Shizuoka, Japan

[8] Kyorin Univ, Dept Med Oncol, Fac Med, Mitaka, Tokyo, Japan

[9] Aichi Canc Ctr Hosp, Dept Gastroenterol, Nagoya, Aichi, Japan

[10] Univ Tokyo Hosp, Dept Gastroenterol, Bunkyo ku, Tokyo, Japan

[11] Osaka Int Canc Inst, Div Hepatobiliary & Pancreat Oncol, Osaka, Osaka, Japan

[12] Japanese Fdn Canc Res, Dept Hepatobiliary Pancreat Med, Canc Inst Hosp, Koto ku, Tokyo, Japan

[13] Yokohama City Univ, Med Ctr, Gastroenterol Ctr, Yokohama, Kanagawa, Japan

[14] Niigata City Gen Hosp, Dept Gastroenterol Surg, Niigata, Niigata, Japan

[15] Yokohama City Univ, Sch Med, Dept Biostat, Yokohama, Kanagawa, Japan

来源：

CLINICAL CANCER RESEARCH | 2024年 / 30卷 / 18期

关键词：

EXPRESSION; LAT1;

D O I：

10.1158/1078-0432.CCR-24-0461

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/m(2)/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.

引用

页码：3990 / 3995

页数：6

共 18 条

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