Evidence map›Paper›PMID 24485879›Full record

SynthesisThe Lancet. Oncology2014

Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials.

Keith T Flaherty, Michael Hennig, Sandra J Lee, Paolo A Ascierto, Reinhard Dummer, Alexander M M Eggermont, Axel Hauschild, Richard Kefford, John M Kirkwood, Georgina V Long and 7 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 7 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

30 citing papers in PubMed, 7 syntheses or guidelines pooled it, 68 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Lag3: From Bench to Bedside.Cancer treatment and research · 2022
    Review
  16. Review
  17. Review
  18. Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 17 institutions in 7 countries.

Keith T FlahertyCenter for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Michael HennigBiostatistics and Epidemiology, GlaxoSmithKline, Munich, Germany.
Sandra J LeeDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Paolo A AsciertoUnit of Melanoma, Cancer Immunotherapy and Innovative Therapy-Istituto Nazionale Tumori Fondazione "G Pascale", Napoli, Italy.
Reinhard DummerDepartment of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Alexander M M EggermontGustave Roussy Cancer Campus, Paris-Sud University Grand Paris, Villejuif, France.
Axel HauschildDepartment of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, University Hospital Kiel, Kiel, Germany.
Richard KeffordWestmead Hospital and Melanoma Institute Australia, University of Sydney, NSW, Australia.
John M KirkwoodSkin Cancer Program University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Georgina V LongMelanoma Institute Australia and the University of Sydney, Sydney, NSW, Australia.
Paul LoriganInstitute of Cancer Sciences, Faculty of Medical & Human Sciences, University of Manchester, Manchester, UK.
Andreas MackensenDepartment of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
Grant McArthurPeter MacCallum Cancer Institute, St Andrews Place, East Melbourne, VIC, Australia.
Steven O'DayBeverly Hills Cancer Center, Beverly Hills, CA, USA.
Poulam M PatelAcademic Unit of Oncology, University of Nottingham, Nottingham, UK.
Caroline RobertDermatology and INSERM Unit 981 Gustave Roussy Cancer Campus and Paris-Sud University Grand Paris, Villejuif, France.
Dirk SchadendorfDepartment of Dermatology, University Hospital Essen, Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de.
Beverly Hills Cancer Center · USDana-Farber Cancer Institute · USEssen University Hospital · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGlaxoSmithKline (Germany) · DEInserm · FRIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · ITMassachusetts General Hospital · USMelanoma Institute Australia · AUPeter MacCallum Cancer Centre · AUThe University of Sydney · AUUniversité Paris-Sud · FRUniversity Hospital of Zurich · CHUniversity of Lübeck · DEUniversity of Manchester · GBUniversity of Nottingham · GBUPMC Hillman Cancer Center · US

Funding

Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
NCI NIH HHS P50 CA121973
6 · The paper itself

Abstract

backgroundRecent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials.

methodsWe systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose.

findingsAfter screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0·71 (95% CI 0·29-0·90) with a random-effects assumption, 0·85 (0·59-0·95) with a fixed-effects assumption, and 0·89 (0·68-0·97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0·96 (0·81-0·99), which decreased to 0·93 (0·74-0·98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0·55, 0·03-0·84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0·85 (0·51-0·96).

interpretationPFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials.

fundingNone.

Indexed as

Randomized Controlled Trials as TopicAntineoplastic Agents, AlkylatingBiomarkersDacarbazineDisease-Free SurvivalHumansMelanomaAntineoplastic Agents, AlkylatingBiomarkersDacarbazine

Identifiers

PMID24485879
PMCPMC4443445
OpenAlexW2116046724

What OpenQuestion holds

Textmetadata
LicenceTDM
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.