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Amol Akhade: KEYNOTE-905 – Potential Practice Changer in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

Amol Akhade/hiranandanihospital.org

Aug 13, 2025, 15:20

Amol Akhade: KEYNOTE-905 – Potential Practice Changer in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on LinkedIn:

“KEYNOTE-905 (EV-303): Potential Practice Changer in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

For years, patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy have faced a stark reality — surgery alone, with no proven systemic therapy to improve survival. Despite radical cystectomy, recurrence rates are high and prognosis remains poor.

That may be about to change.

Merck has announced positive Phase 3 results from KEYNOTE-905 (also known as EV-303), evaluating pembrolizumab + enfortumab vedotin given both before and after surgery (radical cystectomy) vs surgery alone.

Key findings (topline):

Event-Free Survival: Statistically significant and clinically meaningful improvement (primary endpoint)
Overall Survival: Significant benefit
Pathologic Complete Response rate: Higher with combination therapy

Why this matters:

First positive Phase 3 trial to show that systemic therapy in the perioperative setting improves survival in cisplatin-ineligible MIBC. Establishes a new treatment option for a group historically excluded from neoadjuvant chemo trials. Combines immunotherapy (pembrolizumab) and an antibody-drug conjugate (enfortumab vedotin) — potentially synergistic in eliminating micrometastatic disease and preventing recurrence.

Questions moving forward:

Will the magnitude of OS benefit be strong enough to redefine standard of care globally? How manageable is the toxicity profile in the perioperative window? (e.g., rash, neuropathy, hyperglycemia) Will biomarker analysis (PD-L1, Nectin-4) guide patient selection?

If peer-reviewed publication confirms these findings, KEYNOTE-905 could mark a paradigm shift in how we approach bladder cancer in patients unable to receive cisplatin.

Your thoughts: Is the perioperative IO+ADC approach the future in uro-oncology? How might this influence surgical decision-making and trial design in other solid tumors?”

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