Evidence map›Paper›PMID 26378224›Full record

SynthesisJournal of the National Cancer Institute2015

Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval.

Denis L Jardim, Denis L Fontes Jardim, Maria Schwaederle, Caimiao Wei, J Jack Lee, David S Hong, Alexander M Eggermont, Richard L Schilsky, John Mendelsohn, Vladimir Lazar and 1 more

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

Synthesis in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 100 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 5 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

100 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  10. Impact of next-generation sequencing on routine clinical practice and patient inclusion in molecularly targeted clinical trials: a retrospective cohort analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  19. Perioperative Tailored Treatments for Gastric Cancer: Times Are Changing.International journal of molecular sciences · 2023
    Review
  20. Article

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Denis L JardimDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM). rkurzrock@ucsd.edu jardimde@gmail.com.
Denis L Fontes JardimDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM). rkurzrock@ucsd.edu jardimde@gmail.com.
Maria SchwaederleDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
Caimiao WeiDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
J Jack LeeDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
David S HongDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
Alexander M EggermontDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
Richard L SchilskyDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
John MendelsohnDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
Vladimir LazarDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM).
Razelle KurzrockDepartment of Clinical Medicine, Hemocentro da Unicamp, University of Campinas, Sao Paulo, Brazil (DLFJ); Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil (DLFJ); Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA (MS, RK); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX (CW, JJL); Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX (DSH); Department of Functional Genomics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France (AME, VL); Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France (AME, RLS, JM, VL, RK); American Society of Clinical Oncology, Alexandria, VA (RLS); The University of Texas MD Anderson Cancer Center, Houston, TX (JM). rkurzrock@ucsd.edu jardimde@gmail.com.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
6 · The paper itself

Abstract

backgroundIn order to ascertain the impact of a biomarker-based (personalized) strategy, we compared outcomes between US Food and Drug Administration (FDA)-approved cancer treatments that were studied with and without such a selection rationale.

methodsAnticancer agents newly approved (September 1998 to June 2013) were identified at the Drugs@FDA website. Efficacy, treatment-related mortality, and hazard ratios (HRs) for time-to-event endpoints were analyzed and compared in registration trials for these agents. All statistical tests were two-sided.

resultsFifty-eight drugs were included (leading to 57 randomized [32% personalized] and 55 nonrandomized trials [47% personalized], n = 38 104 patients). Trials adopting a personalized strategy more often included targeted (100% vs 65%, P < .001), oral (68% vs 35%, P = .001), and single agents (89% vs 71%, P = .04) and more frequently permitted crossover to experimental treatment (67% vs 28%, P = .009). In randomized registration trials (using a random-effects meta-analysis), personalized therapy arms were associated with higher relative response rate ratios (RRRs, compared with their corresponding control arms) (RRRs = 3.82, 95% confidence interval [CI] = 2.51 to 5.82, vs RRRs = 2.08, 95% CI = 1.76 to 2.47, adjusted P = .03), longer PFS (hazard ratio [HR] = 0.41, 95% CI = 0.33 to 0.51, vs HR = 0.59, 95% CI = 0.53 to 0.65, adjusted P < .001) and a non-statistically significantly longer OS (HR = 0.71, 95% CI = 0.61 to 0.83, vs HR = 0.81, 95% CI = 0.77 to 0.85, adjusted P = .07) compared with nonpersonalized trials. Analysis of experimental arms in all 112 registration trials (randomized and nonrandomized) demonstrated that personalized therapy was associated with higher response rate (48%, 95% CI = 42% to 55%, vs 23%, 95% CI = 20% to 27%, P < .001) and longer PFS (median = 8.3, interquartile range [IQR] = 5 vs 5.5 months, IQR = 5, adjusted P = .002) and OS (median = 19.3, IQR = 17 vs 13.5 months, IQR = 8, Adjusted P = .04). A personalized strategy was an independent predictor of better RR, PFS, and OS, as demonstrated by multilinear regression analysis. Treatment-related mortality rate was similar for personalized and nonpersonalized trials.

conclusionsA biomarker-based approach was safe and associated with improved efficacy outcomes in FDA-approved anticancer agents.

Indexed as

Biomarkers, TumorDrug ApprovalMolecular Targeted TherapyAntineoplastic AgentsClinical Trials as TopicHumansUnited StatesUnited States Food and Drug AdministrationAntineoplastic AgentsBiomarkers, Tumor

Identifiers

PMID26378224
PMCPMC4857149

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.