Evidence map›Paper›PMID 34301751›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2021

RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non-Small Cell Lung Cancer.

Kazuhiko Nakagawa, Ernest Nadal, Edward B Garon, Makoto Nishio, Takashi Seto, Nobuyuki Yamamoto, Keunchil Park, Jin-Yuan Shih, Luis Paz-Ares, Bente Frimodt-Moller and 4 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 3 pooled it
5.0field-weighted citation impact, top 4% 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.

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

33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. OsimertinibTranslational lung cancer research · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Article
  13. Article
  14. Article
  15. Article
  16. RELAY, Erlotinib Plus Ramucirumab in Untreated,JTO clinical and research reports · 2024
    Article
  17. Article
  18. Review
  19. Current status of molecular diagnostics for lung cancer.Exploration of targeted anti-tumor therapy · 2024
    Review
  20. Review
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 13 institutions in 8 countries.

Kazuhiko NakagawaDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Ernest NadalDepartment of Medical Oncology, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID 0000-0002-9674-5554
Edward B GaronDavid Geffen School of Medicine at University of California Los Angeles/TRIO-US Network, Los Angeles, California.ORCID 0000-0001-7077-8801
Makoto NishioThe Cancer Institute Hospital of JFCR, Tokyo, Japan.ORCID 0000-0003-4969-4165
Takashi SetoKyushu Cancer Center, Fukuoka, Japan.ORCID 0000-0002-2960-4364
Nobuyuki YamamotoWakayama Medical University Hospital, Wakayama, Japan.ORCID 0000-0002-7342-0853
Keunchil ParkSamsung Medical Center, Seoul, South Korea.ORCID 0000-0002-4846-7449
Jin-Yuan ShihDepartment of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
Luis Paz-AresHospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Universidad Complutense & CiberOnc, Madrid, Spain.
Bente Frimodt-MollerEli Lilly and Company, Copenhagen, Denmark.
Annamaria H ZimmermannEli Lilly and Company, Indianapolis, Indiana.
Sameera WijayawardanaEli Lilly and Company, Indianapolis, Indiana.
Carla Visseren-GrulLilly Oncology, Utrecht, the Netherlands.
Martin ReckLungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.ORCID 0000-0002-5348-4462
Eli Lilly (United States) · USBristol-Myers Squibb (South Korea) · KRCowi (Denmark) · DKEli Lilly (Netherlands) · NLGerman Center for Lung Research · DEHospital Universitario 12 De Octubre · ESInstitut Català d'Oncologia · ESKindai University Hospital · JPNational Hospital Organization Kyushu Cancer Center · JPNational Taiwan University Hospital · TWThe Cancer Institute Hospital · JPUniversity of California, Los Angeles · USWakayama Medical University · JP

Funding

Eli LillyEli Lilly and CompanyJohn Bilbruck of ProScribe - Envision Pharma Group
6 · The paper itself

Abstract

purposeIn EGFR-mutated metastatic non-small cell lung cancer (NSCLC), outcomes from EGFR tyrosine kinase inhibitors have differed historically by mutation type present, with lower benefit reported in patients with ex21L858R versus ex19del mutations. We investigated if EGFR-activating mutation subtypes impact treatment outcomes in the phase III RELAY study. Associations between EGFR mutation type and preexisting co-occurring and treatment-emergent genetic alterations were also explored. PATIENTS AND

methodsPatients with metastatic NSCLC, an EGFR ex19del or ex21L858R mutation, and no central nervous system metastases were randomized (1:1) to erlotinib (150 mg/day) with either ramucirumab (10 mg/kg; RAM+ERL) or placebo (PBO+ERL), every 2 weeks, until RECIST v1.1-defined progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary and exploratory endpoints included overall response rate (ORR), duration of response (DOR), PFS2, time-to-chemotherapy (TTCT), safety, and next-generation sequencing analyses.

resultsPatients with ex19del and ex21L858R mutations had similar clinical characteristics and comutational profiles. One-year PFS rates for ex19del patients were 74% for RAM+ERL versus 54% for PBO+ERL; for ex21L858R rates were 70% (RAM+ERL) versus 47% (PBO+ERL). Similar treatment benefits (ORR, DOR, PFS2, and TTCT) were observed in RAM+ERL-treated patients with ex19del and ex21L858R. Baseline TP53 comutation was associated with superior outcomes for RAM+ERL in both ex19del and ex21L858R subgroups. EGFR T790M mutation rate at progression was similar between treatment arms and by mutation type.

conclusionsRAM+ERL provided significant clinical benefit for both EGFR ex19del and ex21L858R NSCLC, supporting this regimen as suitable for patients with either of these EGFR mutation types.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsErbB ReceptorsErlotinib HydrochlorideHumansMutationProtein Kinase InhibitorsRamucirumabAntibodies, Monoclonal, HumanizedEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideProtein Kinase InhibitorsRamucirumab

Identifiers

PMID34301751
PMCPMC9662911
OpenAlexW3185217833

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.