Evidence map›Paper›PMID 37390764›Full record

Trial reportESMO open2023

Ramucirumab plus erlotinib versus placebo plus erlotinib in previously untreated EGFR-mutated metastatic non-small-cell lung cancer (RELAY): exploratory analysis of next-generation sequencing results.

E B Garon, M Reck, K Nishio, J V Heymach, M Nishio, S Novello, L Paz-Ares, S Popat, S Ponce Aix, H Graham and 4 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in ESMO open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02411448 (A Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.1field-weighted citation impact, top 6% 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.

NCT02411448 phase3active not recruitingnot on this map

A Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer

TypeinterventionalSponsorEli Lilly and CompanyRan2015 to 2026Enrolled545ConditionsMetastatic Non-Small Cell Lung CancerArmsRamucirumab, Placebo, Erlotinib, Gefitinib, Osimertinib
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

14 authors at 8 institutions in 5 countries.

E B GaronDavid Geffen School of Medicine at University of California Los Angeles/TRIO-US Network, Los Angeles, USA. Electronic address: egaron@mednet.ucla.edu.
M ReckLungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
K NishioDepartment of Medical Oncology, Kindai University, Osaka, Japan.
J V HeymachDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, USA; Department of Cancer Biology, University of Texas, MD Anderson Cancer Center, Houston, USA.
M NishioDepartment of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
S NovelloDepartment of Oncology, AOU San Luigi, University of Turin, Turin, Italy.
L Paz-AresMedical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
S PopatRoyal Marsden NHS Trust, London, UK.
S Ponce AixHospital Universitario 12 de Octubre, Madrid, Spain.
H GrahamEli Lilly and Company, Indianapolis, USA.
B D ButtsEli Lilly and Company, Indianapolis, USA.
C Visseren-GrulEli Lilly and Company, Indianapolis, USA.
K NakagawaDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
RELAY study investigators
Eli Lilly (United States) · USHospital Universitario 12 De Octubre · ESKindai University · JPGerman Center for Lung Research · DEJapanese Foundation For Cancer Research · JPThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · USUniversity of Turin · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRamucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identify clinically relevant alterations in circulating tumor DNA (ctDNA) and explore their impact on treatment outcomes. PATIENTS AND

methodsEligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks. Liquid biopsies were to be prospectively collected at baseline, cycle 4 (C4), and postdiscontinuation follow-up. EGFR and co-occurring/treatment-emergent (TE) genomic alterations in ctDNA were analyzed using Guardant360 NGS platform.

resultsIn those with valid baseline samples, detectable activating EGFR alterations in ctDNA (aEGFR+) were associated with shorter PFS [aEGFR+: 12.7 months (n = 255) versus aEGFR-: 22.0 months (n = 131); hazard ratio (HR) = 1.87, 95% confidence interval (CI) 1.42-2.51]. Irrespective of detectable/undetectable baseline aEGFR, RAM + ERL was associated with longer PFS versus PBO + ERL [aEGFR+: median PFS (mPFS) = 15.2 versus 11.1 months, HR = 0.63, 95% CI 0.46-0.85; aEGFR-: mPFS = 22.1 versus 19.2 months, HR = 0.80, 95% CI 0.49-1.30]. Baseline alterations co-occurring with aEGFR were identified in 69 genes, most commonly TP53 (43%), EGFR (other than aEGFR; 25%), and PIK3CA (10%). PFS was longer in RAM + ERL, irrespective of baseline co-occurring alterations. Clearance of baseline aEGFR by C4 was associated with longer PFS (mPFS = 14.1 versus 7.0 months, HR = 0.481, 95% CI 0.33-0.71). RAM + ERL improved PFS outcomes, irrespective of aEGFR mutation clearance. TE gene alterations were most commonly in EGFR [T790M (29%), other (19%)] and TP53 (16%).

conclusionsBaseline aEGFR alterations in ctDNA were associated with shorter mPFS. RAM + ERL was associated with improved PFS outcomes, irrespective of detectable/undetectable aEGFR, co-occurring baseline alterations, or aEGFR+ clearance by C4. aEGFR+ clearance by C4 was associated with improved PFS outcomes. Monitoring co-occurring alterations and aEGFR+ clearance may provide insights into mechanisms of EGFR tyrosine kinase inhibitor resistance and the patients who may benefit from intensified treatment schedules.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsErbB ReceptorsErlotinib HydrochlorideHigh-Throughput Nucleotide SequencingHumansMutationProtein Kinase InhibitorsRamucirumabEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideProtein Kinase InhibitorsRamucirumabbiomarkersEGFRerlotinibnext-generation sequencingNSCLCramucirumab

Identifiers

PMID37390764
PMCPMC10485403
OpenAlexW4382360851

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.