Top Line: Cisplatin has been the perioperative standard for eligible patients with muscle-invasive bladder cancer for over two decades.
The Study: But following the recent publication of KEYNOTE-905, it’s been tempting to raise the threshold for “cisplatin-eligble” in order to lower the eligibility for the blockbuster perioperative regimen of enfortumab vedotin plus pembrolizumab. Now there’s no need to quibble about platinum eligibility. The phase 3 KEYNOTE-B15 randomized 808 cisplatin-eligible patients with cT2–T4a muscke-invasive bladder cancer to standard neoadjuvant cisplatin/gemcitabine followed by cystectomy versus perioperative enfortumab + pembro (4 neoadjuvant cycles plus an addition 9 months of post-operative adjuvant therapy). Pathologic complete response nearly doubled from 33% to 56%. Two-year event-free survival improved from 66% to 79% (HR 0.53), with an early overall survival benefit (HR 0.65). Toxicity reflected the different regimens: more pruritus and diarrhea with enfortumab + pembro, and more drops in counts with cis/gem. This is all great, but patients are still asking: is there a commonsense approach to bladder preservation and de-escalation of prolonged adjuvant therapy when over half of patients have no residual disease following an initial 4 cycles of enfortumab + pembro..?
TBL: Enfortumab + pembro may soon span the entire perioperative muscle-invasive bladder population or–even more intriguingly–prove an avenue for achieving more successful bladder preservation cases. | Glasky, N Engl J Med 2026
The Study: But following the recent publication of KEYNOTE-905, it’s been tempting to raise the threshold for “cisplatin-eligble” in order to lower the eligibility for the blockbuster perioperative regimen of enfortumab vedotin plus pembrolizumab. Now there’s no need to quibble about platinum eligibility. The phase 3 KEYNOTE-B15 randomized 808 cisplatin-eligible patients with cT2–T4a muscke-invasive bladder cancer to standard neoadjuvant cisplatin/gemcitabine followed by cystectomy versus perioperative enfortumab + pembro (4 neoadjuvant cycles plus an addition 9 months of post-operative adjuvant therapy). Pathologic complete response nearly doubled from 33% to 56%. Two-year event-free survival improved from 66% to 79% (HR 0.53), with an early overall survival benefit (HR 0.65). Toxicity reflected the different regimens: more pruritus and diarrhea with enfortumab + pembro, and more drops in counts with cis/gem. This is all great, but patients are still asking: is there a commonsense approach to bladder preservation and de-escalation of prolonged adjuvant therapy when over half of patients have no residual disease following an initial 4 cycles of enfortumab + pembro..?
TBL: Enfortumab + pembro may soon span the entire perioperative muscle-invasive bladder population or–even more intriguingly–prove an avenue for achieving more successful bladder preservation cases. | Glasky, N Engl J Med 2026