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

Autor:	O'Donnell PH; University of Chicago, Chicago, IL., Milowsky MI; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC., Petrylak DP; Yale Cancer Center, New Haven, CT., Hoimes CJ; Duke Cancer Institute, Duke University, Durham, NC., Flaig TW; University of Colorado Comprehensive Cancer Center, Aurora, CO., Mar N; University of California at Irvine, Irvine, CA., Moon HH; Kaiser Permanente Southern California, Riverside, CA., Friedlander TW; University of California at San Francisco, San Francisco, CA., McKay RR; University of California at San Diego, San Diego, CA., Bilen MA; Emory University Winship Cancer Institute, Atlanta, GA., Srinivas S; Stanford Cancer Center, Stanford, CA., Burgess EF; Levine Cancer Center, Charlotte, NC., Ramamurthy C; University of Texas Health Sciences Center at San Antonio, San Antonio, TX., George S; Roswell Park Cancer Center, Buffalo, NY., Geynisman DM; Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA., Bracarda S; Azienda Ospedaliera Santa Maria di Terni, Terni, Italy., Borchiellini D; Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Geoffrois L; Institut de Cancerologie de Lorraine, Vandoeuvre Les Nancy, France., Maroto Rey JP; Hospital de la Santa Creu i Sant Paul, Barcelona, Spain., Ferrario C; Jewish General Hospital, Montreal, Quebec, Canada., Carret AS; Seagen Inc, Bothell, WA., Yu Y; Seagen Inc, Bothell, WA., Guseva M; Astellas Pharma, Northbrook, IL., Homet Moreno B; Merck & Co Inc, Rahway, NJ., Rosenberg JE; Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Sep 01; Vol. 41 (25), pp. 4107-4117. Date of Electronic Publication: 2023 Jun 27.
DOI:	10.1200/JCO.22.02887
Abstrakt:	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.
Databáze:	MEDLINE
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