Evidence map›Paper›PMID 24220220›Full record

SynthesisClinical genitourinary cancer2014

Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma.

Neeraj Agarwal, Joaquim Bellmunt, Benjamin L Maughan, Kenneth M Boucher, Toni K Choueiri, Angela Q Qu, Nicholas J Vogelzang, Ronan Fougeray, Guenter Niegisch, Peter Albers and 12 more

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

Synthesis in Clinical genitourinary cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 6% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Review
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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

22 authors at 17 institutions in 5 countries.

Neeraj AgarwalDepartment of Internal Medicine/Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Joaquim BellmuntUniversity Hospital del Mar-IMIM, Barcelona, Spain.
Benjamin L MaughanDepartment of Internal Medicine/Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Kenneth M BoucherDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Toni K ChoueiriDepartment of Medicine/Solid Tumor Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
Angela Q QuDepartment of Medicine/Solid Tumor Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
Nicholas J VogelzangComprehensive Cancer Centers of Nevada, Las Vegas, NV.
Ronan FougerayInstitut de Recherche Pierre Fabre, Boulogne, France.
Guenter NiegischDepartment of Urology, Heinrich Heine University, Dusseldorf, Germany.
Peter AlbersDepartment of Urology, Heinrich Heine University, Dusseldorf, Germany.
Yu-Ning WongDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
Yoo-Joung KoDepartment of Medicine, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
Srikala S SridharDepartment of Medicine, Princess Margaret Hospital, Toronto, ON, Canada.
Srinivas K TantravahiDepartment of Internal Medicine/Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Matthew D GalskyDepartment of Medicine/Hematology and Medical Oncology, Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY.
Daniel P PetrylakDepartment of Internal Medicine/Medical Oncology, Yale University Cancer Center, New Haven, CT.
Ulka N VaishampayanDepartment of Oncology, Wayne State University, Detroit, MI.
Amitkumar N MehtaDepartment of Medicine/Hematology-Oncology, UAB Comprehensive Cancer Center, Birmingham, AL.
Tomasz M BeerDepartment of Medicine/Hematology-Oncology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR.
Cora N SternbergDepartment of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
Jonathan E RosenbergDepartment of Medicine/Hematology-Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Guru SonpavdeDepartment of Medicine/Hematology-Oncology, UAB Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
University of Utah · USHarvard University · USHeinrich Heine University Düsseldorf · DECarlo Forlanini Hospital · ITComprehensive Cancer Centers of Nevada · USFox Chase Cancer Center · USHuntsman Cancer Institute · USIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · USOregon Health & Science University · USPierre Fabre (France) · FRPrincess Margaret Cancer Centre · CASunnybrook Health Science Centre · CASylvester Comprehensive Cancer Center · USUniversity of Alabama at Birmingham · USWayne State University · USYale Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
Enhancing neoadjuvant chemotherpay responses with targeted T cellsR01CA140314 · NCI · WAYNE STATE UNIVERSITY · PI BEPLER, GEROLD · 2010 to 2015
$2.5M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA022453NCI NIH HHS R01 CA140314
6 · The paper itself

Abstract

objectiveSecond-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents.

methodsTen second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction.

resultsIn the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R(2) = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R(2) = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared stronger than the correlation of response (76%, Қ = 0.17) with OS12 in the external validation dataset.

conclusionsPFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC.

Indexed as

Carcinoma, Transitional CellClinical Trials, Phase II as TopicDisease-Free SurvivalHumansProportional Hazards ModelsTreatment OutcomeUrinary Bladder NeoplasmsAdvanced urothelial carcinomaIntermediate endpointOverall survivalProgression-free survival at 6 monthsSecond-line treatment

Identifiers

PMID24220220
PMCPMC4142680
OpenAlexW2029168581

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.