Evidence map›Paper›PMID 31050707›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2019

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

Y Fradet, J Bellmunt, D J Vaughn, J L Lee, L Fong, N J Vogelzang, M A Climent, D P Petrylak, T K Choueiri, A Necchi and 10 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02256436 (A Phase III Randomized Clinical Trial of Pembrolizumab), which is not on this map. Cited by 270 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
270citing papers in PubMed, 12 pooled it
59.2field-weighted citation impact, top 1% 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.

NCT02256436 phase3completednot on this map

A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2014 to 2020Enrolled542ConditionsUrothelial CancerArmspembrolizumab, paclitaxel, vinflunine, docetaxel
3 · Its place in the literature

Who cites it

270 citing papers in PubMed, 12 syntheses or guidelines pooled it, 478 citations in OpenAlex.

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  5. Immunotherapy for advanced or metastatic urothelial carcinoma.The Cochrane database of systematic reviews · 2023
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210 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 18 institutions in 8 countries.

Y FradetDepartment of Surgery/Urology, CHU de Québec-Université Laval, Québec City, Canada. Electronic address: yves.fradet@crchudequebec.ulaval.ca.
J BellmuntDepartment of Medical Oncology, PSMAR-IMIM Research Institute, Barcelona, Spain and Harvard Medical School University, Boston, USA.
D J VaughnDepartment of Medical Oncology, Abramson Cancer Center, Perelman Center for Advanced Medicine, Philadelphia, USA.
J L LeeDepartment of Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea.
L FongDepartment of Medicine and Urology, University of California San Francisco, San Francisco.
N J VogelzangDepartment of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, USA.
M A ClimentDepartment of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
D P PetrylakDivision of Medical Oncology, Smilow Cancer Hospital at Yale University, New Haven.
T K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
A NecchiDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
W GerritsenDepartment of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
H GurneyDepartment of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, NSW, Australia.
D I QuinnDepartment of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA.
S CulineDepartment of Medical Oncology, Hôpital Saint-Louis, Paris, France.
C N SternbergDepartment of Medical Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York.
K NamDepartment of Medical Oncology, Merck & Co., Inc., Kenilworth, USA.
T L FrenklDepartment of Medical Oncology, Merck & Co., Inc., Kenilworth, USA.
R F PeriniDepartment of Medical Oncology, Merck & Co., Inc., Kenilworth, USA.
R de WitDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
D F BajorinDepartment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USAbramson Cancer CenterAsan Medical Center · KRComprehensive Cancer Centers of Nevada · USCornell University · USDana-Farber Cancer Institute · USErasmus MC Cancer Institute · NLFondazione IRCCS Istituto Nazionale dei Tumori · ITFundación Instituto Valenciano de Oncología · ESHôpital Saint-Louis · FRMemorial Sloan Kettering Cancer Center · USMunicipal Institute for Medical Research · ESRadboud University Medical Center · NLUniversité Laval · CAUniversity of California, San Francisco · USUniversity of Southern California · USWestmead Hospital · AUYale University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. PATIENTS AND

methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.

resultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.

conclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.

trial registrationClinicalTrials.gov: NCT02256436.

Indexed as

AdultAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsDocetaxelFollow-Up StudiesHumansNeoplasm Recurrence, LocalPaclitaxelPrognosisResponse Evaluation Criteria in Solid TumorsSurvival RateUrologic NeoplasmsVinblastineAntibodies, Monoclonal, HumanizedDocetaxelPaclitaxelpembrolizumabVinblastinevinfluninePD-1PD-L1pembrolizumaburothelial cancer

Identifiers

PMID31050707
PMCPMC6594457
OpenAlexW2943108118

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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.