03556nam a2200277   4500001000800000007000300008008004100011040000800052041000800060100003700068245007800105300002300183520263500206650004102841650002102882650003802903650003302941700003502974700002703009700002503036700002803061700003103089773011003120942003103230999001703261ESSALUDta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aGalsky, Matthew D.eAutor953782  aEnfortumab vedotin and pembrolizumab in cisplatin-eligible bladder cancer  apáginas: 338-348  aBackground: Neoadjuvant cisplatin-based chemotherapy is a standard therapy for muscle-invasive bladder cancer. The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin–pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear. 
Methods: We conducted a phase 3, open-label, randomized trial involving adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph-node dissection (cystectomy). Participants were assigned to receive neoadjuvant enfortumab vedotin–pembrolizumab (4 cycles; enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] and pembrolizumab [200 mg on day 1] every 3 weeks), cystectomy, and 5 cycles of enfortumab vedotin and 13 cycles of pembrolizumab as adjuvant therapy or to receive neoadjuvant cisplatin–gemcitabine (4 cycles; cisplatin [70 mg per square meter of body-surface area on day 1] plus gemcitabine [1000 mg per square meter on days 1 and 8] every 3 weeks) and cystectomy. The primary end point was event-free survival; key secondary end points were overall survival and pathological complete response. Safety was assessed. Results: A total of 405 participants were assigned to receive enfortumab vedotin–pembrolizumab and 403 to receive cisplatin–gemcitabine. The median time from randomization to the data-cutoff date was 33.6 months (range, 22.5 to 53.6). A total of 86.7% of the participants in the enfortumab vedotin–pembrolizumab group and 89.6% of those in the cisplatin–gemcitabine group underwent cystectomy. At 2 years, estimated event-free survival was 79.4% with enfortumab vedotin–pembrolizumab and 66.2% with cisplatin–gemcitabine (hazard ratio for an event or death, 0.53; 95% confidence interval [CI], 0.41 to 0.70; P<0.001); estimated overall survival was 86.9% and 81.3%, respectively (hazard ratio for death, 0.65; 95% CI, 0.48 to 0.89; two-sided P=0.006). A pathological complete response occurred in 55.8% and 32.5% of the participants (P<0.001). The incidence of grade 3 or higher adverse events of any cause was 75.7% with enfortumab vedotin–pembrolizumab and 67.2% with cisplatin–gemcitabine. Conclusions: Among participants with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy, perioperative enfortumab vedotin–pembrolizumab led to significantly better event-free and overall survival outcomes and a significantly higher incidence of pathological complete response than neoadjuvant cisplatin–gemcitabine, but with more adverse events of grade 3 or higher.  aENFERMEDADES DE LA PRÓSTATA953783  aUROLOGÍA96502  aTRATAMIENTO EN ONCOLOGÍA953713  aCANCER GENITOURINARIO953654  aValderrama, Begoña P.953784  aMaruzzo, Marco 953785  aFont, Albert 953786  aCiuleanu, Tudor 953787  aChatzkel, Jonathan 9537880 022717922637dMassachusetts NEJM GroupoNEJM004tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-07-31zSQB  c22745d22745