Evidence map›Paper›PMID 35029306›Full record

Trial reportBritish journal of clinical pharmacology2022

Exposure-response relationship of ramucirumab in RANGE, a randomized phase III trial in advanced urothelial carcinoma refractory to platinum therapy.

Ronald de Wit, Thomas Powles, Daniel Castellano, Andrea Necchi, Jae-Lyun Lee, Michiel S van der Heijden, Nobuaki Matsubara, Aristotelis Bamias, Aude Fléchon, Cora N Sternberg and 8 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02426125 (A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therapy), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02426125 phase3completednot on this map

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therapy

TypeinterventionalSponsorEli Lilly and CompanyRan2015 to 2022Enrolled530ConditionsUrothelial CarcinomaArmsRamucirumab, Docetaxel, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 14 institutions in 10 countries.

Ronald de WitErasmus MC Cancer Institute, Rotterdam, the Netherlands.
Thomas PowlesBarts Cancer Institute, Queen Mary University of London, UK.
Daniel CastellanoHospital 12 de Octubre, I + 12 Research Institute, Madrid, Spain.
Andrea NecchiVita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy.
Jae-Lyun LeeAsan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Michiel S van der HeijdenNetherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Nobuaki MatsubaraNational Cancer Center Hospital East, Chiba, Japan.
Aristotelis BamiasNational and Kapodistrian University of Athens, Athens, Greece.
Aude FléchonCentre Léon Bérard, Lyon, France.
Cora N SternbergEnglander Institute for Precision Medicine, Weill Cornell Medicine, Sandra and Edward Meyer Cancer Center, New York, NY, USA.
Alexandra DrakakiUniversity of California Los Angeles, Los Angeles, CA, USA.
Evan Y YuUniversity of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA.
Annamaria H ZimmermannEli Lilly and Company, Indianapolis, IN, USA.
Amanda LongEli Lilly and Company, Indianapolis, IN, USA.
Richard A WalgrenEli Lilly and Company, Indianapolis, IN, USA.
Ling GaoEli Lilly and Company, Indianapolis, IN, USA.
Katherine M Bell-McGuinnEli Lilly and Company, Indianapolis, IN, USA.
Daniel P PetrylakYale University School of Medicine, New Haven, CT, USA.
Eli Lilly (United States) · USCentre Léon Bérard · FRErasmus MC Cancer Institute · NLFred Hutch Cancer Center · USLander Institute · ILNational and Kapodistrian University of Athens · GRNational Cancer Center Hospital East · JPNetherlands Cancer Institute-Antoni van Leeuwenhoek Hospital · NLQueen Mary University of London · GBResearch Institute Hospital 12 de Octubre · ESUniversity of California, Los Angeles · USUniversity of Ulsan · KRVita-Salute San Raffaele University · ITYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

aimsPatients with advanced urothelial carcinoma (UC) who progress after platinum-based chemotherapy have a poor prognosis, and there is a medical need to improve current treatment options. Ramucirumab plus docetaxel significantly improved progression-free survival but not overall survival (OS) in platinum-refractory advanced UC (RANGE trial; NCT02426125). Here, we report the exposure-response (ER) of ramucirumab plus docetaxel using data from the RANGE trial.

methodsPharmacokinetic (PK) samples were collected (cycle 1-3, 5, 9 [day 1] and 30 days from treatment discontinuation), and PK data were analysed using population PK (popPK) analysis. The minimum ramucirumab concentration after first dose administration (C

resultsSeveral poor prognostic factors (ECOG 1, haemoglobin concentration <100 g/L, presence of liver metastases) appeared more frequently in the lower exposure quartiles, suggesting a possible disease-PK interaction. A significant association was identified between C

conclusionsThis prespecified ER analyses suggests a positive relationship between efficacy and ramucirumab exposure, with an imbalance associated with disease prognostic factors. Further investigation may elucidate a possible disease-PK relationship.

Indexed as

Carcinoma, Transitional CellUrinary Bladder NeoplasmsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsDocetaxelHumansPlatinumRamucirumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDocetaxelPlatinumRamucirumabexposure-responseoverall survivalprogression-free survivalramucirumaburothelial carcinoma

Identifiers

PMID35029306
PMCPMC9302693
OpenAlexW4205385339

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.