2. Academic Validation
  3. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

  • J Clin Oncol. 2023 Sep 1;41(25):4107-4117. doi: 10.1200/JCO.22.02887.
Peter H O'Donnell 1,  Matthew I Milowsky 2,  Daniel P Petrylak 3,  Christopher J Hoimes 4,  Thomas W Flaig 5,  Nataliya Mar 6,  Helen H Moon 7,  Terence W Friedlander 8,  Rana R McKay 9,  Mehmet A Bilen 10,  Sandy Srinivas 11,  Earle F Burgess 12,  Chethan Ramamurthy 13,  Saby George 14,  Daniel M Geynisman 15,  Sergio Bracarda 16,  Delphine Borchiellini 17,  Lionnel Geoffrois 18,  Jose Pablo Maroto Rey 19,  Christiano Ferrario 20,  Anne-Sophie Carret 21,  Yao Yu 21,  Maria Guseva 22,  Blanca Homet Moreno 23,  Jonathan E Rosenberg 24
Affiliations

Affiliations

  • 1 University of Chicago, Chicago, IL.
  • 2 University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
  • 3 Yale Cancer Center, New Haven, CT.
  • 4 Duke Cancer Institute, Duke University, Durham, NC.
  • 5 University of Colorado Comprehensive Cancer Center, Aurora, CO.
  • 6 University of California at Irvine, Irvine, CA.
  • 7 Kaiser Permanente Southern California, Riverside, CA.
  • 8 University of California at San Francisco, San Francisco, CA.
  • 9 University of California at San Diego, San Diego, CA.
  • 10 Emory University Winship Cancer Institute, Atlanta, GA.
  • 11 Stanford Cancer Center, Stanford, CA.
  • 12 Levine Cancer Center, Charlotte, NC.
  • 13 University of Texas Health Sciences Center at San Antonio, San Antonio, TX.
  • 14 Roswell Park Cancer Center, Buffalo, NY.
  • 15 Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.
  • 16 Azienda Ospedaliera Santa Maria di Terni, Terni, Italy.
  • 17 Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France.
  • 18 Institut de Cancerologie de Lorraine, Vandoeuvre Les Nancy, France.
  • 19 Hospital de la Santa Creu i Sant Paul, Barcelona, Spain.
  • 20 Jewish General Hospital, Montreal, Quebec, Canada.
  • 21 Seagen Inc, Bothell, WA.
  • 22 Astellas Pharma, Northbrook, IL.
  • 23 Merck & Co Inc, Rahway, NJ.
  • 24 Memorial Sloan Kettering Cancer Center, New York, NY.
PMID: 37369081 DOI: 10.1200/JCO.22.02887
Abstract

Purpose: Patients with locally advanced or metastatic urothelial Cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial Cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.

Patients and methods: In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.

Results: The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).

Conclusion: EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.

Figures
Products