Enfortumab Vedotin with or Without Pembrolizumab in Cisplatin-Ineligible Patients with Previously Untreated Locally Advanced or Metastatic Urothelial Cancer
O'Donnell, Peter H. (University of Chicago)
Milowsky, Matthew I. (University of North Carolina)
Petrylak, Daniel P. (Yale Cancer Center)
Hoimes, Christopher J. (Duke University)
Flaig, Thomas W. (University of Colorado Comprehensive Cancer Center)
Mar, Nataliya (University of California at Irvine)
Moon, Helen H. (Kaiser Permanente Southern California)
Friedlander, Terence W. (University of California at San Francisco)
McKay, Rana R. (University of California at San Diego)
Bilen, Mehmet A. (Winship Cancer Institute)
Srinivas, Sandy (Stanford Cancer Center)
Burgess, Earle F. (Levine Cancer Center)
Ramamurthy, Chethan (University of Texas Health Sciences Center at San Antonio)
George, Saby (Roswell Park Cancer Center)
Geynisman, Daniel M. (Fox Chase Cancer Center)
Bracarda, S. (Azienda Ospedaliera Santa Maria di Terni)
Borchiellini, Sergio (Université Côte d'Azur)
Geoffrois, Lionnel (Institut de Cancerologie de Lorraine)
Maroto Rey, Pablo (Institut d'Investigació Biomèdica Sant Pau)
Ferrario, Christiano (Jewish General Hospital)
Carret, Anne-Sophie (Seagen Inc)
Yu, Yao (Seagen Inc Rahway, NJ)
Guseva, Maria (Astellas Pharma)
Homet Moreno, Blanca (Merck & Co Inc)
Rosenberg, Jonathan E. (Memorial Sloan Kettering Cancer Center)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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. 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. 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%). CONCLUSIONEV + 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antibodies, Monoclonal, Humanized ; Carcinoma, Transitional Cell ; Cisplatin ; Humans
Publicat a:	Journal of clinical oncology, Vol. 41 Núm. 25 (january 2023) , p. 4107-4117, ISSN 1527-7755

DOI: 10.1200/JCO.22.02887
PMID: 37369081

18 p, 1.1 MB

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