Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study

Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition...

Full description

Saved in:
Bibliographic Details
Published in:The lancet oncology 2021-10, Vol.22 (10), p.1468-1482
Main Authors: Valle, Juan W, Vogel, Arndt, Denlinger, Crystal S, He, Aiwu Ruth, Bai, Li-Yuan, Orlova, Rashida, Van Cutsem, Eric, Adeva, Jorge, Chen, Li-Tzong, Obermannova, Radka, Ettrich, Thomas J, Chen, Jen-Shi, Wasan, Harpreet, Girvan, Allicia C, Zhang, Wei, Liu, Jiangang, Tang, Chunlao, Ebert, Philip J, Aggarwal, Amit, McNeely, Samuel C, Moser, Brian A, Oliveira, Joana M, Carlesi, Roberto, Walgren, Richard A, Oh, Do-Youn
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - drug therapy
Adenocarcinoma - mortality
Adenocarcinoma - secondary
Adverse events
Aged
Angiogenesis
Angiogenesis Inhibitors - administration & dosage
Angiogenesis Inhibitors - adverse effects
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - adverse effects
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Biliary tract
Biliary Tract Neoplasms - drug therapy
Biliary Tract Neoplasms - mortality
Biliary Tract Neoplasms - pathology
Cancer therapies
Chemotherapy
Cholangiocarcinoma
Cisplatin
Clinical trials
Disease Progression
Double-Blind Method
Double-blind studies
Drug Administration Schedule
Embolism
FDA approval
Female
Gemcitabine
Humans
Immunotherapy
Indazoles - administration & dosage
Indazoles - adverse effects
Intravenous administration
Kinases
Life span
Lung cancer
Male
Medical prognosis
Metastases
Metastasis
Middle Aged
Monoclonal antibodies
Neutropenia
Niacinamide - administration & dosage
Niacinamide - adverse effects
Niacinamide - analogs & derivatives
Patients
Placebos
Progression-Free Survival
Protein Kinase Inhibitors - administration & dosage
Protein Kinase Inhibitors - adverse effects
Ramucirumab
Response rates
Safety
Sepsis
Solid tumors
Survival
Targeted cancer therapy
Thrombocytopenia
Time Factors
Toxicity
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition to first-line cisplatin–gemcitabine in patients with locally advanced or metastatic biliary tract cancer. We did a randomised, double-blind, phase 2 study at 81 hospitals across 18 countries. We enrolled patients with histologically or cytologically confirmed, non-resectable, recurrent, or metastatic biliary tract adenocarcinoma, who were treatment-naive, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, estimated life expectancy of 3 months or more, and measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1. Eligible participants were randomly assigned (2:1:2:1) to receive either intravenous ramucirumab 8 mg/kg or placebo (on days 1 and 8 in 21-day cycles) or oral merestinib 80 mg or placebo (once daily) until disease progression, unacceptable toxicity, death, or patient or investigator request for discontinuation. All participants received intravenous cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 (on days 1 and 8 in 21-day cycles), for a maximum of eight cycles. Randomisation was done by an interactive web response system using a permuted block method (blocks of six) and was stratified by primary tumour site, geographical region, and presence of metastatic disease. Participants, investigators, and the study funder were masked to treatment assignment within the intravenous and oral groups. The primary endpoint was investigator-assessed progression-free survival (in the intention-to-treat population). The safety analysis was done in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02711553, and long-term follow-up is ongoing. Between May 25, 2016, and Aug 8, 2017, 450 patients were assessed for eligibility and 309 (69%) were enrolled and randomly assigned to ramucirumab (n=106), merestinib (n=102), or pooled placebo (n=101); 306 received at least one dose of study treatment. The median follow-up time for progression-free survival at data cutoff (Feb 16, 2018) was 10·9 months (IQR 8·1–14·1). Median progression-free survival was 6·5 months (80% CI 5·7–7·1) in the ramucirumab group, 7·0 months (6·2–7·1) in the meresti
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(21)00409-5