Evidence map›Paper›PMID 34865086›Full record

ReviewJournal of the National Cancer Institute2022

Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology.

Richard M Goldberg, Richard Adams, Marc Buyse, Cathy Eng, Axel Grothey, Thierry André, Alberto F Sobrero, Stuart M Lichtman, Al B Benson, Cornelis J A Punt and 17 more

Abstract readReview
In one paragraph

Review in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Trial
  3. Article
  4. 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

27 authors.

Richard M GoldbergWest Virginia University Cancer Institute, Morgantown, WV, USA.ORCID 0000-0003-0308-8223
Richard AdamsCardiff University and Velindre UNHS Trust, UK.ORCID 0000-0003-3915-7243
Marc BuyseInternational Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium.ORCID 0000-0002-4559-0994
Cathy EngVanderbilt-Ingram Cancer Center, Nashville, TN, USA.ORCID 0000-0003-2335-0612
Axel GrotheyWest Cancer Center and Research Institute, Germantown, TN, USA.ORCID 0000-0002-9341-6499
Thierry AndréHôpital Saint Antoine, Paris, France.ORCID 0000-0002-5103-7095
Alberto F SobreroOspedale S. Martin, Genova, Italy.
Stuart M LichtmanMemorial Sloan Kettering Cancer Center, NY, USA.
Al B BensonRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
Cornelis J A PuntUniversity Medical Centre Utrecht, the Netherlands.
Tim MaughanGray Institute of Radiation Oncology and Biology, University of Oxford, UK.ORCID 0000-0002-0580-5065
Tomasz BurzykowskiInternational Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium.ORCID 0000-0003-3378-975X
Dirkje SommeijerUniversity of Amsterdam Academic Medical Centre and Flevohospital, Almere, the Netherlands.
Everardo D SaadInternational Drug  Development Institute (IDDI), Louvain-la-Neuve, Belgium.ORCID 0000-0003-4039-588X
Qian ShiMayo Clinic, Rochester, MN, USA.ORCID 0000-0002-4640-8832
Elisabeth CoartInternational Drug Development  Institute (IDDI), Louvain-la-Neuve, Belgium.
Benoist ChibaudelHôpital Franco-Britannique, Paris, France.
Miriam KoopmanUniversity Medical Centre Utrecht, the Netherlands.ORCID 0000-0003-1550-1978
Hans-Joachim SchmollMartin Luther University, Halle, Germany.ORCID 0000-0001-8705-0593
Takayuki YoshinoNational Cancer  Center Hospital East, Kashiwa, Japan.
Julien TaiebGeorges Pompidou European Hospital, Paris, France.ORCID 0000-0002-9955-4753
Niall C TebbuttAustin  Health, Heidelberg, Victoria, Australia.ORCID 0000-0003-2613-5168
John ZalcbergMonash University, School of Public Health, Australia.ORCID 0000-0002-6624-0782
Josep TaberneroVall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Barcelona, Spain.ORCID 0000-0002-2495-8139
Eric Van CutsemUniversity Hospital Gasthuisberg, Leuven, Belgium.ORCID 0000-0002-6372-1230
Alastair MathesonFondation ARCAD, Paris, France.
Aimery de GramontHôpital  Franco-Britannique, Paris, France.ORCID 0000-0001-7940-9877

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Cancer Research UK 25350NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research.

Indexed as

Colorectal NeoplasmsNeoplasms, Second PrimaryClinical Trials, Phase III as TopicDatabases, FactualHumansMeta-Analysis as TopicResearch DesignTreatment Outcome

Identifiers

PMID34865086
PMCPMC9194619

What OpenQuestion holds

Textmetadata
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.