Evidence map›Paper›PMID 36041086›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2023

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer.

Christopher J Hoimes, Thomas W Flaig, Matthew I Milowsky, Terence W Friedlander, Mehmet Asim Bilen, Shilpa Gupta, Sandy Srinivas, Jaime R Merchan, Rana R McKay, Daniel P Petrylak and 5 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04223856 (An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer), which is not on this map. Cited by 174 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 11 pooled it
51.9field-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.

NCT04223856 phase3active not recruitingnot on this map

An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

TypeinterventionalSponsorAstellas Pharma Global Development, Inc.Ran2020 to 2028Enrolled886ConditionsUrothelial CancerArmsEnfortumab vedotin, Pembrolizumab, Cisplatin, Carboplatin, Gemcitabine
3 · Its place in the literature

Who cites it

174 citing papers in PubMed, 11 syntheses or guidelines pooled it, 250 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. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

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

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

15 authors at 14 institutions in 1 country.

Christopher J HoimesDuke Cancer Institute, Duke University, Durham, NC.ORCID 0000-0001-8980-2410
Thomas W FlaigUniversity of Colorado Comprehensive Cancer Center, Aurora, CO.ORCID 0000-0001-6145-9040
Matthew I MilowskyUniversity of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC.ORCID 0000-0002-8965-8129
Terence W FriedlanderUniversity of California San Francisco Medical Center, San Francisco, CA.ORCID 0000-0002-3630-4941
Mehmet Asim BilenWinship Cancer Institute of Emory University, Atlanta, GA.
Shilpa GuptaTaussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH.ORCID 0000-0002-8775-503X
Sandy SrinivasStanford University Medical Center, Stanford, CA.
Jaime R MerchanUniversity of Miami, Miami, FL.ORCID 0000-0003-3752-4134
Rana R McKayUniversity of California San Diego, San Diego, CA.ORCID 0000-0002-0581-7963
Daniel P PetrylakYale Cancer Center, New Haven, CT.ORCID 0000-0001-6165-5797
Carolyn SasseAstellas, Northbrook, IL.ORCID 0000-0001-5883-7477
Blanca Homet MorenoMerck & Co, Inc, Kenilworth, NJ.
Yao YuSeagen Inc, Bothell, WA.
Anne-Sophie CarretSeagen Inc, Bothell, WA.ORCID 0000-0001-6723-6948
Jonathan E RosenbergMemorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.ORCID 0000-0003-2637-4249
Seagen (United States) · USAstellas Pharma (United States) · USCleveland Clinic · USEmory University · USMemorial Sloan Kettering Cancer Center · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USStanford Medicine · USUniversity Hospitals of Cleveland · USUniversity of California San Diego · USUniversity of California San Francisco Medical Center · USUniversity of Colorado Cancer Center · USUniversity of Miami · USUniversity of North Carolina at Chapel Hill · USYale Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
TRANSLATIONAL RESEARCH ONCOLOGY TRAINING GRANTK12CA076917 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI GERSON, STANTON L. · 1997 to 2022
$14.2M
NCI NIH HHS K12 CA076917NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

purposeCisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many patients with la/mUC are ineligible. Each enfortumab vedotin and pembrolizumab have shown a survival benefit versus chemotherapy in UC, are not restricted by cisplatin eligibility, and warrant investigation as a first-line (1L) combination therapy in patients ineligible for cisplatin.

methodsIn this ongoing phase Ib/II, multicenter, open-label study, 1L cisplatin-ineligible patients with la/mUC received enfortumab vedotin 1.25 mg/kg once daily on days 1 and 8 and pembrolizumab 200 mg (day 1) intravenously once daily in 3-week cycles. The primary end point was safety. Key secondary end points included confirmed objective response rate, duration of response (DOR), and overall survival (OS).

resultsForty-five patients received enfortumab vedotin plus pembrolizumab. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (55.6%), fatigue (51.1%), and alopecia (48.9%). Twenty-nine patients (64.4%) had grade 3 or higher TRAEs; the most common were increased lipase (17.8%), maculopapular rash (11.1%), and fatigue (11.1%). One death (2.2%) was classified as a TRAE. The confirmed objective response rate after a median of nine cycles was 73.3% with a complete response rate of 15.6%. The median DOR and median OS were 25.6 months and 26.1 months, respectively.

conclusionEnfortumab vedotin plus pembrolizumab showed a manageable safety profile. Most patients experienced tumor shrinkage. The median DOR and median OS exceeding 2 years in a cisplatin-ineligible patient population make this a promising combination currently under investigation in a phase III study (ClinicalTrials.gov identifier: NCT04223856).

Indexed as

CisplatinNeoplasmsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsHumansAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCisplatinenfortumab vedotinpembrolizumab

Identifiers

PMID36041086
PMCPMC10476837
OpenAlexW4293698156

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.