Evidence map›Paper›PMID 32702645›Full record

ReviewEuropean journal of cancer (Oxford, England : 1990)2020

Progression-free survival is a suboptimal predictor for overall survival among metastatic solid tumour clinical trials.

Dario Pasalic, Gwendolyn J McGinnis, C David Fuller, Aaron J Grossberg, Vivek Verma, Walker Mainwaring, Austin B Miller, Timothy A Lin, Amit Jethanandani, Andres F Espinoza and 11 more

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European journal of cancer (Oxford, England : 1990), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 5 pooled it
2.2field-weighted citation impact, top 11% 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

39 citing papers in PubMed, 5 syntheses or guidelines pooled it, 66 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

21 authors at 9 institutions in 2 countries.

Dario PasalicThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gwendolyn J McGinnisThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
C David FullerThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Aaron J GrossbergOregon Health & Science University, Portland, OR, USA.
Vivek VermaAllegheny Health Network Cancer Institute, Pittsburgh, PA, USA.
Walker MainwaringBaylor College of Medicine, Houston, TX, USA.
Austin B MillerThe University of Texas Health Science Center, McGovern Medical School, Houston, TX, USA.
Timothy A LinThe Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Amit JethanandaniThe University of Tennessee Health Science Center, Memphis, TN, USA.
Andres F EspinozaBaylor College of Medicine, Houston, TX, USA.
Markus DiefenhardtUniversity of Frankfurt, Frankfurt, Germany; Frankfurt Cancer Institute, Frankfurt, Germany.
Prajnan DasThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vivek SubbiahThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ishwaria M SubbiahThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Reshma JagsiUniversity of Michigan, Ann Arbor, MI, USA.
Adam S GardenThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Emmanouil FokasUniversity of Frankfurt, Frankfurt, Germany; Frankfurt Cancer Institute, Frankfurt, Germany; German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, Frankfurt, Germany.
Claus RödelUniversity of Frankfurt, Frankfurt, Germany; Frankfurt Cancer Institute, Frankfurt, Germany; German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, Frankfurt, Germany.
Charles R ThomasOregon Health & Science University, Portland, OR, USA.
Bruce D MinskyThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ethan B LudmirThe University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ebludmir@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USGoethe University Frankfurt · DEBaylor College of Medicine · USOregon Health & Science University · USAllegheny Health Network · USJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USUniversity of Michigan · USUniversity of Tennessee Health Science Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Fellow and Resident Radiation Oncology iNtensive Training in Imaging and Informatics to Empower Research Careers (FRONTI2ER)R25EB025787 · NIBIB · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAS, PRAJNAN, FULLER, CLIFTON DAVID · 2018 to 2022
$535k
NCI NIH HHS P30 CA016672NIBIB NIH HHS R25 EB025787
6 · The paper itself

Abstract

backgroundThe use of overall survival (OS) as the gold standard primary end-point (PEP) in metastatic oncologic randomised controlled trials (RCTs) has declined in favour of progression-free survival (PFS) without a complete understanding of the degree to which PFS reliably predicts for OS.

methodsUsing ClinicalTrials.gov, we identified 1239 phase III oncologic RCTs, 260 of which were metastatic solid tumour trials with a superiority-design investigating a therapeutic intervention by using either a PFS or OS PEP. Each individual trial was reviewed to quantify RCT design factors and disease-related outcomes.

resultsA total of 172,133 patients were enrolled from the year 1999 to 2015 in RCTs that used PFS (56.2%, 146/260) or OS (43.8%, 114/260) as the PEP. PFS trials were more likely to restrict patient eligibility by using molecular criteria (15.1% versus 4.4%, p = 0.005) use targeted therapy (80.1% versus 67.5%, p = 0.048), accrue fewer patients (median 495 versus 619, p = 0.03), and successfully meet the trial PEP (66.9% versus 33.3%, p < 0.0001). On multiple binary logistic regression analysis, factors that predicted for PFS or OS PEP trial success included choice of PFS PEP (p < 0.0001), molecular profile restriction (p = 0.02) and single agent therapy (p = 0.02). Notably, there was only a 38% (31/82) conversion rate of positive PFS-to-OS benefit; lack of industry sponsorship predicted for PFS-to-OS signal conversion (80.0% without industry sponsorship versus 35.1% with industry sponsorship, p = 0.045).

conclusionsA PFS PEP has suboptimal positive predictive value for OS among phase III metastatic solid tumour RCTs. Regulatory agency decisions should be judicious in using PFS results as the primary basis for approval.

Indexed as

BiomarkersClinical Trials, Phase III as TopicComparative Effectiveness ResearchEquivalence Trials as TopicHumansNeoplasm MetastasisNeoplasmsPredictive Value of TestsPrognosisProgression-Free SurvivalRandomized Controlled Trials as TopicResearch DesignSurvival AnalysisTreatment OutcomeBiomarkersAccelerated approvalClinical efficacyClinically meaningful end-pointCorrelateIndirect measureMetastatic cancerMetastatic diseaseRandomised clinical trialsReplacement end-pointSurrogate end-point

Identifiers

PMID32702645
PMCPMC7702022
OpenAlexW3042531629

What OpenQuestion holds

Textmetadata
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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.