Evidence map›Paper›PMID 25584489›Full record

Trial reportBritish journal of cancer2015

Exposure-response analysis of rilotumumab in gastric cancer: the role of tumour MET expression.

M Zhu, R Tang, S Doshi, K S Oliner, S Dubey, Y Jiang, R C Donehower, T Iveson, E Y Loh, Y Zhang

Abstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Trial
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  11. Article
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  15. Review
  16. MET-targeted therapy for gastric cancer: the importance of a biomarker-based strategy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2016
    Review
  17. MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2016
    Article
  18. Review
  19. Article
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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

10 authors.

M ZhuTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
R TangTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
S DoshiTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
K S OlinerTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
S DubeyGlobal Clinical Development, Amgen Inc., South San Francisco, CA, USA.
Y JiangTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
R C DonehowerOncology, Johns Hopkins Medical Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
T IvesonMedical Oncology, University Hospital Southampton, Southampton, UK.
E Y LohGlobal Clinical Development, Amgen Inc., South San Francisco, CA, USA.
Y ZhangTranslational Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRilotumumab, an investigational, monoclonal antibody, inhibits MET-mediated signalling. In a randomized phase 2 trial of rilotumumab±epirubicin/cisplatin/capecitabine in gastric or oesophagogastric junction cancer, patients receiving rilotumumab showed a trend towards improved survival, especially in MET-positive patients, but no clear dose-response relationship was observed. Exposure-response and biomarker analyses were used for dose selection and to differentiate patient subpopulations that may benefit most from treatment. Here, we analyse rilotumumab exposure-survival and exposure-safety and the impact of MET expression on these relationships.

methodsIndividual rilotumumab exposure parameters were generated using population pharmacokinetic modelling. Relationships among rilotumumab dose (7.5 and 15 mg kg(-1)), exposure, and clinical outcomes (progression-free survival (PFS) and overall survival (OS)) were evaluated with Cox regression models and Kaplan-Meier plots. MET status and other baseline covariates were evaluated in subgroup and multivariate analyses. Treatment-emergent adverse events were summarised by exposure.

resultsAmong MET-positive patients, higher rilotumumab exposure, vs placebo and low exposure, was associated with improved median PFS (80% CI: 7.0 (5.7-9.7) vs 4.4 (2.9-4.9) and 5.5 (4.2-6.8) months) and OS (13.4 (10.6-18.6) vs 5.7 (4.7-10.2) and 8.1 (6.9-11.1) months) without increased toxicity. No rilotumumab benefit was seen among MET-negative patients.

conclusionsRilotumumab had an exposure-dependent treatment effect in patients with MET-positive gastric or oesophagogastric junction cancer.

Indexed as

AdenocarcinomaAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisProto-Oncogene Proteins c-metStomach NeoplasmsTreatment OutcomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedMET protein, humanProto-Oncogene Proteins c-metrilotumumab

Identifiers

PMID25584489
PMCPMC4453660

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LicenceCC BY-NC-SA
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Registered trials

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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.