Padcev/Keytruda extends survival in early bladder cancer

Pfizer and Astellas reckon they have new data for Padcev in bladder cancer that could extend its use into earlier-stage disease, and help the drug meet lofty sales projections.

In the EV-303/KEYNOTE-905 study, the combination of nectin-4-directed antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) with MSD's PD-1 inhibitor Keytruda (pembrolizumab) improved overall survival when used before and after surgery in patients with muscle-invasive bladder cancer (MIBC) who were not eligible for cisplatin chemotherapy.

The study of neoadjuvant/adjuvant use of the regimen marks the first time that a systemic treatment has improved survival in this patient group, according to lead investigator Christof Vulsteke of Integrated Cancer Centre Ghent (IKG) in Belgium.

These patients "have not seen any treatment advance beyond surgery and face high rates of disease recurrence and a poor prognosis, even after having their bladder removed," he said.

Astellas and Pfizer have said they plan to submit the data for approval with regulators around the world to try to extend the label for Padcev, which is already approved in combination with Keytruda to treat previously untreated patients with locally advanced or metastatic urothelial carcinoma (UC), the most common form of bladder cancer, regardless of cisplatin eligibility.

The two partners are also running a second phase 3 trial of neoadjuvant/adjuvant Padcev/Keytruda in MIBC (EV-304/KEYNOTE-B15) in the hope of extending use into the cisplatin-eligible patient population as well.

Last year, Astellas hiked its peak sales expectations for Padcev from $2.7 billion to $3.4 billion on the promise of extending its use in bladder cancer, and there are already signs of an acceleration with Pfizer reporting sales rose 32% to $967 million in the first half of 2025, driven primarily by increased market share in first-line UC indication.

Pfizer books Padcev sales in the Americas after its takeover of Seagen, which partnered with Astellas on the ADC's development, while Astellas records revenues in other markets. In its fiscal first-quarter results posted at the end of July, Astellas recorded a 45% increase in Padcev sales to JPY 55.5 billion (around $370 million).

"Padcev plus Keytruda has already changed the treatment paradigm for patients with locally advanced or metastatic urothelial cancer as standard of care," said Johanna Bendel, Pfizer's head of oncology development.

"These latest results underscore the practice-changing potential of this combination in earlier stages of bladder cancer, where it has the potential to improve outcomes for even more patients."

Other options have also recently been approved for neoadjuvant/adjuvant therapy of MIBC that can be treated with surgery, including AstraZeneca's PD-L1 inhibitor Imfinzi (durvalumab) given in combination with platinum chemotherapy before surgery to remove the bladder and as a monotherapy afterwards.