Merck & Co. has moved closer to a significant European expansion for Keytruda after the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended Keytruda plus Padcev for adults with resectable muscle-invasive bladder cancer before and after surgery regardless of whether patients are eligible for cisplatin chemotherapy. The September 17 opinion now goes to the European Commission, with Merck expecting a final decision during the fourth quarter of 2026. If approved, the regimen would become the first PD-1 inhibitor plus antibody-drug conjugate combination available for this broader perioperative muscle-invasive bladder cancer population in the European Union.
The recommendation is backed by the Phase 3 KEYNOTE-B15, also known as EV-304, study, where perioperative Keytruda plus Padcev reduced the risk of disease progression, recurrence or death by 47% compared with neoadjuvant gemcitabine-cisplatin chemotherapy followed by surgery. The combination also reduced the risk of death by 35%, while 55.8% of patients achieved a pathologic complete response compared with 32.5% receiving chemotherapy. Those results make the regulatory development more than an incremental label extension because they challenge a long-established chemotherapy-based treatment pathway in patients healthy enough to receive cisplatin.
The European Commission decision would also complete an important geographic expansion already underway elsewhere. The United States Food and Drug Administration approved Keytruda plus Padcev in July 2026 for perioperative treatment of adults with muscle-invasive bladder cancer regardless of cisplatin eligibility. Europe had previously approved the combination in June for cisplatin-ineligible patients based on the separate KEYNOTE-905 study, meaning the latest recommendation would effectively remove the cisplatin-eligibility restriction and open the regimen to a substantially broader surgical population.
Why could the KEYNOTE-B15 result change how muscle-invasive bladder cancer is treated?
Muscle-invasive bladder cancer represents roughly one-quarter of newly diagnosed bladder cancer cases and carries a meaningful risk of recurrence even when patients undergo potentially curative surgery. Merck said more than 635,000 people are diagnosed with bladder cancer globally each year, including approximately 224,700 in Europe based on 2022 estimates. Nearly half of patients receiving the traditional approach of cisplatin-based chemotherapy followed by radical cystectomy can eventually experience recurrence, illustrating why treatment before and after surgery has become such an important development target.
KEYNOTE-B15 enrolled cisplatin-eligible patients, making the comparator particularly meaningful. Rather than testing the Keytruda-Padcev combination against surgery alone or an obviously weaker treatment, the trial compared it with gemcitabine plus cisplatin, the established neoadjuvant chemotherapy approach for patients capable of tolerating platinum therapy. Event-free-survival events occurred in 87 of 405 patients assigned to Keytruda plus Padcev compared with 146 of 403 receiving chemotherapy, producing the hazard ratio of 0.53 that underpins the 47% relative risk reduction.
The overall survival result strengthens the case considerably because earlier-stage oncology trials can sometimes improve recurrence-related endpoints without yet demonstrating that patients live longer. Deaths occurred in 17% of patients in the experimental group compared with 25% in the chemotherapy group at the reported analysis, corresponding to a hazard ratio of 0.65 and a statistically significant 35% reduction in death risk. Merck has now demonstrated overall survival improvement with Keytruda-based therapy across several earlier-stage cancer settings, reinforcing its strategy of moving immunotherapy upstream from metastatic disease into potentially curative treatment.
What does the 55.8% pathologic complete response rate tell physicians?
Pathologic complete response means no residual invasive cancer is found in the surgically removed tissue after preoperative therapy. In KEYNOTE-B15, that occurred in 55.8% of patients receiving Keytruda plus Padcev compared with 32.5% receiving gemcitabine-cisplatin, a difference of more than 23 percentage points. For clinicians, that provides direct evidence that the combination is producing substantially deeper tumor eradication before bladder removal, although long-term survival remains the more consequential endpoint.
The result also helps explain why combining a PD-1 inhibitor with an antibody-drug conjugate has generated so much interest across oncology. Keytruda removes inhibitory signaling that can restrain anti-tumor immune responses, while Padcev uses an antibody directed against Nectin-4 to deliver a cytotoxic payload to cancer cells. The objective is to combine immune-mediated attack with targeted drug delivery rather than simply intensifying conventional chemotherapy.
Padcev is being developed through collaborations involving Astellas Pharma and Pfizer, while Keytruda belongs to Merck & Co. The KEYNOTE-B15 study itself was conducted through collaboration among Merck & Co., Pfizer and Astellas Pharma, and Astellas Pharma Europe is the European marketing authorization holder for Padcev. That means any European expansion carries strategic significance across several large pharmaceutical companies rather than benefiting Merck & Co. alone.
Could Keytruda plus Padcev replace cisplatin chemotherapy for many eligible patients?
The data establish a strong efficacy argument, but adoption will also depend on toxicity, patient characteristics, physician experience and health-system economics. Keytruda plus Padcev introduces a different adverse-event profile from platinum chemotherapy rather than eliminating treatment burden altogether. In KEYNOTE-B15, commonly reported adverse reactions included rash in 63% of patients, fatigue in 48%, itching in 46%, peripheral neuropathy in 43%, diarrhea in 36% and alopecia in 32%, while 20% experienced hyperglycemia.
The perioperative setting makes safety particularly important because the objective is cure and patients still need to reach radical cystectomy safely after neoadjuvant treatment. Serious adverse reactions occurred in 27% of patients during the neoadjuvant phase, and 13 of 403 patients did not proceed to surgery because of adverse reactions. Among the 351 combination-treated patients who underwent cystectomy, 26 experienced a surgery delay exceeding eight weeks because of adverse reactions.
After surgery, serious adverse reactions were reported in 35% of the 249 patients who entered the adjuvant phase, with urinary tract infection, sepsis, diarrhea, hyperglycemia and pneumonitis or interstitial lung disease among the events reported. These findings do not erase the substantial survival and event-free-survival benefits, but they make treatment selection and toxicity management essential parts of the risk-benefit equation. Earlier-stage cancer patients may have decades of potential life ahead of them, so tolerance for avoidable long-term toxicity can be lower than in advanced metastatic disease.
Why is another earlier-stage Keytruda indication strategically important for Merck & Co.?
Keytruda remains by far the largest commercial engine inside Merck & Co. The Keytruda family, including the newer subcutaneous Keytruda Qlex formulation, generated $8.4 billion in second-quarter 2026 sales, up 5% on a reported basis and 4% excluding currency effects. Merck & Co.’s total quarterly revenue was $16.6 billion, meaning Keytruda and Keytruda Qlex alone represented slightly more than half of company-wide sales during the period.
That concentration explains why expanding Keytruda into earlier-stage disease remains strategically critical. Metastatic indications established pembrolizumab as one of the pharmaceutical industry’s largest oncology franchises, but perioperative therapy offers access to patients much earlier in their cancer journey and can extend treatment across both neoadjuvant and adjuvant phases. Merck & Co. says it has more than 30 ongoing registrational studies examining its medicines and pipeline candidates in earlier cancer settings, showing that KEYNOTE-B15 is part of a much larger franchise-development strategy rather than an isolated bladder cancer experiment.
Subcutaneous Keytruda Qlex adds another dimension because European regulators included the subcutaneous formulation in their recommendation. Merck & Co. reported $463 million in Keytruda Qlex sales during the second quarter after launching the formulation in the third quarter of 2025. A formulation that can be administered subcutaneously rather than through conventional intravenous infusion could eventually reduce treatment-chair time and create additional flexibility as Keytruda reaches larger earlier-stage populations.
How large could the European bladder cancer opportunity become?
Europe recorded approximately 224,700 bladder cancer diagnoses and more than 70,300 deaths in 2022, according to figures cited by Merck & Co. If roughly 25% of newly diagnosed cases are muscle invasive, the theoretical population is substantial, although the commercially addressable group will be smaller after accounting for resectability, fitness for surgery, staging, local clinical practice and other factors.
The important expansion is the removal of cisplatin eligibility as a dividing line. Europe already allowed Keytruda plus Padcev around surgery for patients unable to receive cisplatin. KEYNOTE-B15 now provides the evidence required to compete directly with cisplatin-based neoadjuvant chemotherapy among patients who could otherwise receive the traditional regimen.
That creates genuine replacement-growth potential rather than merely additive growth among previously undertreated patients. If physicians increasingly select Keytruda plus Padcev instead of gemcitabine-cisplatin in eligible patients, Merck & Co., Pfizer and Astellas Pharma could capture treatment volume from an established generic chemotherapy pathway while also expanding therapy around the surgical episode.
What does the latest regulatory progress mean for Merck & Co. investor sentiment?
Merck & Co. shares closed at $146.87 on September 18, down 0.19% for the session, but the stock remained up approximately 8.7% over one month, 28.3% over six months and 39.5% since the beginning of 2026. The shares were also trading below their 52-week high of $156.92, suggesting the market has already substantially re-rated Merck & Co. as investors assess pipeline progress, new launches and the company’s ability to broaden growth beyond the mature portions of its portfolio.
The European Keytruda-Padcev recommendation is unlikely to alter company valuation on its own because Merck & Co. already generates tens of billions of dollars in annual revenue and Keytruda has numerous approved indications. Its importance is cumulative. Every earlier-stage cancer indication capable of adding patients, treatment duration or geographic reach strengthens the franchise while Merck & Co. simultaneously attempts to build additional growth engines across oncology, cardiovascular disease, immunology and infectious disease.
The immediate catalyst is now straightforward. The European Commission is expected to make its decision during the fourth quarter of 2026, and approval would allow Keytruda plus Padcev to move from a cisplatin-ineligible niche into the broader resectable muscle-invasive bladder cancer population. After that, the more meaningful test will be adoption: whether European oncologists and urologists view the survival advantage as strong enough to move significant numbers of cisplatin-eligible patients away from a chemotherapy standard that has shaped treatment for years.
