FDA approves PADCEV, KEYTRUDA combination for muscle invasive bladder cancer

The Food and Drug Administration on November 21 approved PADCEV, also known as enfortumab vedotin ejfv, together with KEYTRUDA, or pembrolizumab, as neoadjuvant therapy followed by continued adjuvant treatment after cystectomy for adults with muscle invasive bladder cancer who are ineligible for cisplatin containing chemotherapy. Where indicated the approval also covers KEYTRUDA QLEX, a formulation combining pembrolizumab and berahyaluronidase alfa pmph. The approval was disclosed in a joint press release by Pfizer and Astellas.

Regulators based the decision in part on results from the pivotal Phase 3 EV 303 trial, also called KEYNOTE 905, which the companies said showed substantial reductions in recurrence and death for patients who received the combination therapy versus those who underwent surgery alone. The authorization adds a potentially practice changing option for patients who have had limited perioperative systemic therapy choices because they cannot tolerate standard cisplatin based regimens.

The FDA approval comes with a boxed warning for serious skin reactions, including Stevens Johnson syndrome and toxic epidermal necrolysis. The label details monitoring and management guidance, including recommendations for prompt recognition and discontinuation of therapy in severe cases. The companies said standard safety and prescribing information will accompany the rollout.

Clinicians and hospital systems are now weighing how to integrate an immune conjugate plus checkpoint inhibitor strategy into preoperative care. Patients deemed ineligible for cisplatin often include older adults and those with impaired kidney function, significant hearing loss, peripheral neuropathy, or other comorbidities that make cisplatin unsafe. For these patients the new regimen could reduce the high risk of relapse that historically follows surgery alone, but it will require careful coordination among urologic surgeons, medical oncologists, dermatologists, and perioperative care teams.

Public health experts say the approval underscores both promise and challenge. The regimen could improve survival for a group that has been undertreated, yet it also raises questions about equitable access. Immunotherapy and antibody drug conjugates commonly carry high price tags and complex administration needs, which can create barriers in community hospitals and safety net settings. Rural hospitals and clinics that lack infusion capacity or on site dermatology consultation may struggle to deliver the therapy safely.

Policy makers and insurers will confront decisions about coverage and reimbursement that will determine how widely the option reaches patients on Medicare, Medicaid, and private plans. Advocacy groups have flagged the persistent problem of underrepresentation of older adults and racial and ethnic minorities in clinical trials, an issue that can complicate assessments of benefit and risk in real world populations.

Regulators typically require postmarketing surveillance and risk mitigation measures when approving therapies with serious adverse reaction risks. How effectively those systems detect and manage rare but life threatening skin reactions will be crucial to patient safety.

The approval represents an important advance for a population with limited perioperative options, but translating trial results into equitable outcomes will depend on resources, policy choices, and sustained attention to safety monitoring and community level access.