Enfortumab Vedotin Plus Pembrolizumab Achieves High pCR Rates in MIBC

Enfortumab Vedotin Plus Pembrolizumab Achieves High pCR Rates in MIBC

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Enfortumab vedotin plus pembrolizumab has doubled the pathologic complete response rate in muscle-invasive bladder cancer (MIBC), reshaping bladder preservation approaches for patients too frail for standard chemotherapy. In the KEYNOTE-905/EV-303 trial of 344 cisplatin-ineligible patients, the combination achieved a pCR rate of 57.1% compared to 8.6% with no systemic therapy. For cisplatin-eligible patients in KEYNOTE-B15/EV-304, enfortumab vedotin plus pembrolizumab achieved a pCR in 55.8% of patients, significantly higher than the 32.5% rate seen with cisplatin plus gemcitabine chemotherapy.

Improved Outcomes Enable New Treatment Paradigms

“With chemotherapy alone, about 1 in 3 patients achieved a complete response, whereas urologists can now tell patients roughly 3 in 5 will,” said Meeks. The drugs are better, our chances of getting rid of the cancer are better, so our approach can change. This shift in response rates has prompted a reevaluation of bladder preservation strategies, particularly for patients who may not tolerate radical cystectomy due to functional limitations or personal preferences.

Bladder Preservation Becomes Viable Option for More Patients

Before the advent of these newer regimens, bladder-sparing approaches were largely reserved for patients with poor functional status, those refusing cystectomy, or those unable to tolerate neoadjuvant chemotherapy. Meeks recounted the case of a chef patient who explained that a stoma would make it impossible to work with food, which led to a conversation about bladder preservation. The INTACT (SWOG/NRG S1806) phase 3 trial, which randomly assigns patients with cT2-T4N0M0 MIBC to concurrent chemoradiation with or without atezolizumab, has helped standardize delivery of bladder preservation and built confidence among community urologists in trimodal therapy as a viable option.

KEYNOTE-B15/EV-304: Enfortumab Vedotin Plus Pembrolizumab in Muscle-Invasive Bladder Cancer | GUARD

Response-Guided Algorithm for Treatment Decisions

Meeks detailed his current protocol for managing patients with cT2-cT4b MIBC, which entails sending them to medical oncology for 3 or 4 cycles of enfortumab vedotin plus pembrolizumab, followed by biomarker assessment using PET-CT and ctDNA. Response is then evaluated with blue light cystoscopy, transurethral resection of bladder tumor, and mapping biopsies. For patients with a cT0, ctDNA-negative response, observation is reasonable. Those with cT1, ctDNA-negative disease can be considered for trimodal therapy followed by pembrolizumab. For patients with persistent cT2 or greater disease or ctDNA positivity, radical cystectomy is recommended. Previously, about 60% of patients with a clinical complete response to neoadjuvant chemotherapy who declined cystectomy had a 5-year disease-free survival.

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