A combination of Pfizer and Astellas’ Padcev (enfortumab vedotin) and MSD’s Keytruda (pembrolizumab) has offered significant improvements to patient outcomes compared with standard of care (SoC) chemotherapy in muscle-invasive bladder cancer (MIBC).
During the Phase III EV-304 trial (NCT04700124), the antibody-drug conjugate (ADC) and programmed death ligand 1 (PD-1) inhibitor combination significantly improved event-free survival (EFS) over neoadjuvant platinum chemotherapy – meeting the primary trial endpoint.
This effect was seen when Padcev-Keytruda was administered as an adjuvant and neoadjuvant combination in patients undergoing surgery.
The EV-304 trial also met its secondary endpoint, with patients treated with Padcev-Keytruda experiencing significant improvements in overall survival (OS) compared with those given SoC neoadjuvant chemotherapy.
Alongside its impact on survival and MIBC-related events, Padcev-Keytruda heightened pathological complete response (pCR) rates when used in the neoadjuvant setting only, in comparison with neoadjuvant chemotherapy.
The safety profile of Padcev-Keytruda was consistent with previous studies evaluating the duo.
This makes Padcev-Keytruda the first chemotherapy-free combination to improve EFS and OS in the pre-operative and post-operative setting in cisplatin-eligible patients with MIBC.
According to Pfizer’s chief oncology officer Jeff Legos, the positive outcome of this trial could signify Padcev-Keytruda’s potential to become a platinum-free SoC, which he says could see the combination become the “cornerstone of care for bladder cancer regardless of cisplatin eligibility.”
Based on the Phase III data, Pfizer and Astellas, the co-developers of Padcev, now plan to discuss the results of the EV-304 trial with global regulators, which could see Padcev-Keytruda gain approval for use in MIBC regardless of a patient’s cisplatin eligibility.
The combination got the US Food and Drug Administration (FDA) greenlight as a pre-operative and post-operative adjuvant treatment in cisplatin-ineligible patients with MIBC in November 2025.
GlobalData, parent company of Clinical Trials Arena, estimates that the bladder cancer market will reach $16bn in value across the eight major markets (8MM: the US, France, Germany, Italy, Spain, the UK, China and Japan) in 2033.
Moving away from chemotherapy
Chemotherapy has been the backbone of cancer care for decades, with its use expanding across almost every solid and haematological indication.
While its efficacy has been proven in a wide range of cancers, companies are increasingly looking to move away from this type of treatment in favour of more targeted, effective and tolerable combination treatment options.
A modality showing particular promise is ADCs, with AstraZeneca and Daiichi’s Trop2-targeting ADC, Datroway (datopotamab deruxtecan), having trumped the OS benefits offered by chemotherapy in triple-negative breast cancer patients during the Phase III TROPION-Breast02 trial (NCT05374512).
RemeGen Biosciences’ HER2-focused ADC Aidixi (disitamab vedotin) also offered significant improvements to both progression-free survival (PFS) and OS alongside PD-1 inhibitor toripalimab over chemotherapy. This trend was observed during a China-based Phase III study in first-line metastatic bladder cancer.
According to GlobalData’s Pharmaceutical Intelligence Center, the best-selling ADC in 2024 was Daiichi Sankyo and AstraZeneca’s Enhertu (trastuzumab deruxtecan), which brought in $4.1bn for the pair.
A patient-based forecast from GlobalData predicts that Padcev will generate $3.6bn in sales during 2033 in bladder cancer alone.
