The U.S. Food and Drug Administration expanded the approval of pembrolizumab (Keytruda) and its subcutaneous formulation (Keytruda Qlex), each in combination with enfortumab vedotin (Padcev), to cover all adults with muscle-invasive bladder cancer who are candidates for surgery to remove their bladder, according to the FDA's official announcement on July 10, 2026.
The expansion removes a significant prior restriction: until this approval, the combination was permitted in this surgical setting only for patients who could not safely receive cisplatin, a standard platinum-based chemotherapy drug. The combination is now approved as neoadjuvant therapy given before surgery, followed by continued adjuvant treatment after the bladder is removed, regardless of cisplatin eligibility.
Why This Matters
Muscle-invasive bladder cancer is an aggressive disease in which cancer has grown into the muscle layer of the bladder wall, requiring surgical removal of the bladder in most cases. Before this approval, the standard preoperative regimen for patients who could tolerate it was platinum-based chemotherapy, specifically gemcitabine plus cisplatin. That regimen has not changed meaningfully in decades. Patients who could not tolerate cisplatin, due to kidney dysfunction, hearing loss, peripheral neuropathy, or other factors, had access to the pembrolizumab and enfortumab vedotin combination since November 2025. Patients who were cisplatin-eligible did not.
The July 10 expansion changes that. Every adult with muscle-invasive bladder cancer who is a candidate for cystectomy can now receive the pembrolizumab plus enfortumab vedotin regimen before and after surgery, based on evidence showing it outperforms the previous standard chemotherapy approach. For the approximately 82,300 Americans diagnosed with bladder cancer annually, with many presenting with or progressing to muscle-invasive disease, this represents a meaningful shift in standard of care.
What We Know So Far
The expanded approval is based on results from the Phase 3 KEYNOTE-B15/EV-304 trial, which enrolled 808 patients with previously untreated muscle-invasive bladder cancer who were eligible for cisplatin-based chemotherapy and candidates for radical cystectomy. Patients were randomly assigned to receive neoadjuvant pembrolizumab plus enfortumab vedotin followed by surgery and adjuvant pembrolizumab plus enfortumab vedotin, or neoadjuvant gemcitabine plus cisplatin followed by surgery.
The trial met its primary endpoint of event-free survival, with a hazard ratio of 0.53 compared to the chemotherapy arm, meaning patients in the pembrolizumab plus enfortumab vedotin group had approximately 47 percent lower risk of experiencing disease events including progression, recurrence, or death. The combination also demonstrated an overall survival benefit, with a hazard ratio of 0.65. The pathologic complete response rate, meaning no cancer detectable in the removed bladder at the time of surgery, was 55.8 percent in the combination arm versus 32.5 percent with gemcitabine plus cisplatin.
Urology Times coverage noted that this marks the first time in nearly 25 years that a non-platinum-based regimen has surpassed cisplatin-based neoadjuvant chemotherapy in cisplatin-eligible muscle-invasive bladder cancer. The FDA also separately considered data from the KEYNOTE-905 trial in cisplatin-ineligible patients, which showed an event-free survival hazard ratio of 0.40 and an overall survival hazard ratio of 0.50 compared to immediate surgery.
Where the Impact Is Highest
Bladder cancer is the fourth most common cancer in American men, and treatment requires multidisciplinary teams at major cancer centers as well as community urology and oncology practices. Patients at centers including Memorial Sloan Kettering Cancer Center in New York, MD Anderson Cancer Center in Houston, Johns Hopkins, and the University of Michigan are most likely to receive this regimen early. Community oncology and urology practices, which treat the majority of U.S. cancer patients, will follow as formularies are updated and guidelines are revised.
The availability of a subcutaneous formulation, Keytruda Qlex, which delivers pembrolizumab over one to two minutes rather than the 30-minute intravenous infusion, may improve clinic throughput and flexibility at high-volume cancer centers.
What Doctors and Experts Say
The KEYNOTE-B15 trial results were presented as a late-breaking abstract at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium by lead author Matthew Galsky and colleagues, where the pathologic complete response data and event-free survival improvement were characterized as practice-changing. Merck and Astellas both issued press releases on July 10, 2026, describing the approval as establishing a new cisplatin-independent standard of care for muscle-invasive bladder cancer.
AJMC's clinical reporting noted that the Keytruda Qlex subcutaneous formulation carries identical indications to the intravenous pembrolizumab and maintains the same clinical profile, offering logistical advantages without clinical trade-offs.
What the Evidence Shows and What It Does Not
The KEYNOTE-B15/EV-304 study is a Phase 3 randomized controlled trial in 808 patients published and presented at ASCO GU 2026, with primary results supporting improved event-free survival (HR 0.53), overall survival (HR 0.65), and pathologic complete response (55.8 percent versus 32.5 percent) with perioperative pembrolizumab plus enfortumab vedotin compared to neoadjuvant gemcitabine plus cisplatin. The trial enrolled patients who were eligible for cisplatin, meaning results specifically demonstrate superiority over the prior standard in that population.
What the trial did not evaluate is long-term survival beyond the current follow-up period or outcomes in populations with significant comorbidities that may complicate both the combination regimen and surgery. Readers should know that this regimen requires careful monitoring for immune-mediated adverse events from pembrolizumab and for skin reactions, peripheral neuropathy, hyperglycemia, and ocular effects associated with enfortumab vedotin, all of which are detailed in the prescribing information.
Who Faces the Greatest Risk Without This Option
Patients with cisplatin-eligible muscle-invasive bladder cancer who previously received gemcitabine plus cisplatin as their only preoperative option now have access to a regimen that has demonstrated superior pathologic complete response and event-free survival. Pathologic complete response at the time of surgery is a meaningful intermediate endpoint because patients with residual cancer in the bladder at surgery have a substantially higher risk of recurrence and death. A pathologic complete response rate of 55.8 percent versus 32.5 percent represents a clinically important improvement in the proportion of patients achieving the most favorable surgical outcome.
Symptoms and Warning Signs to Watch For
Pembrolizumab carries the risk of immune-mediated adverse reactions, which can affect virtually any organ system including the lungs, liver, intestines, kidneys, skin, and endocrine glands. Symptoms warranting prompt medical evaluation during treatment include new or worsening shortness of breath, persistent cough, severe diarrhea or abdominal pain, yellowing of the skin or eyes, and rashes. Enfortumab vedotin is associated with severe skin reactions, peripheral neuropathy, and high blood sugar. Patients experiencing any of these symptoms during treatment should contact their oncology team immediately rather than waiting for a scheduled appointment.
What You Can Do Now
Patients recently diagnosed with muscle-invasive bladder cancer should ask their urologist or oncologist whether they are a candidate for radical cystectomy and whether the pembrolizumab plus enfortumab vedotin perioperative regimen is appropriate for their clinical situation. Patients who were previously told they were only eligible for cisplatin-based chemotherapy should specifically ask whether the expanded approval changes their options. The full FDA prescribing information for both Keytruda and Padcev is available at fda.gov.
Cost and Access: What Patients Should Know
Pembrolizumab (Keytruda) and enfortumab vedotin (Padcev) are both branded specialty drugs with high costs. Merck and Astellas maintain patient assistance programs for eligible patients. Commercial insurance and Medicare Part D plans typically cover approved FDA indications for these agents, though prior authorization requirements vary. Patients should work with their cancer center's financial counseling team to navigate coverage and copay assistance.
What Happens Next
The oncology community will update treatment guidelines to reflect the new expanded indication. Clinical trials are ongoing to evaluate the combination in other bladder cancer settings. MedicalDaily will report on further updates to treatment guidelines and additional approval developments as they occur.
The Bottom Line
The FDA's July 10, 2026, expansion of pembrolizumab plus enfortumab vedotin to all muscle-invasive bladder cancer patients before and after surgery, based on the KEYNOTE-B15 trial showing superiority over the prior chemotherapy standard in cisplatin-eligible patients, is a significant oncology milestone. For patients facing a bladder cancer diagnosis, the most important immediate step is discussing this expanded indication with a urologist and oncologist to understand whether it applies to their specific situation.
