At last year’s European Society for Medical Oncology annual meeting, Keytruda and Padcev’s game-changing data set a new standard for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). Now, at ESMO 2026, AstraZeneca is rolling out its own Imfinzi-Padcev combination pitch, hoping to differentiate with a tweaked dosing regimen.
AZ’s Imfinzi and Pfizer and Astellas’ Padcev, used around surgery, slashed the risk of death by 42% versus surgery alone in MIBC patients who were not eligible for or declined cisplatin-based chemotherapy, the phase 3 Volga trial showed.
While strong, the magnitude of the Imfinzi doublet’s overall survival improvement came below the 50% set by Keytruda-Padcev in the landmark EV-303/Keynote-905 trial in a similar cisplatin-ineligible population, although cross-trial comparison has its flaws.
But AZ notably achieved that result with reduced administration of Padcev and the immuno-oncology agent. While the EV-303 regimen uses Padcev both before and after surgery for a total of nine cycles, Volga only gives the Nectin-4-directed antibody-drug conjugate before surgery for three cycles. In AZ’s regimen, Imfinzi is given altogether 12 cycles, including three three-week cycles preoperatively and nine four-week cycles postoperatively. By comparison, Keytruda is used for up to 17, three-week cycles, including three before surgery.
In an interview with Fierce, AZ’s oncology R&D chief, Susan Galbraith, Ph.D., described the data as showing the “transformative potential” of an ADC-IO combo “in a well-tolerated option.”
“Just three cycles of neoadjuvant [Padcev] and then continued maintenance of Imfinzi that we know is well-tolerated, we think this is a patient-centric regimen which can challenge the current standard of care and reinforces the potential for Imfinzi as a backbone therapy across different stages of bladder cancer,” Galbraith said.
Noting that the effect size of a treatment’s relative efficacy is also affected by the performance of the control arm, Galbraith pointed to landmark event-free survival (EFS) and OS data.
At two years, the estimated OS rate was 80% for the Keytruda combo (63% for control) and 78% for the Imfinzi doublet (69% for control) in their separate trials.
The two-year EFS rate numerically favored Keytruda-Padcev, at 75% in EV-303 (39% for control), compared with 64% for Imfinzi-Padcev (45% for control) in Volga. The two trials’ definitions of EFS are largely similar: a negative event includes disease recurrence or progression, failure to undergo radical cystectomy in those with residual disease and death.
In their separate trials, Imfinzi-Padcev significantly improved EFS by 49%, while Keytruda-Padcev logged a 60% EFS benefit.
If the numerically lower EFS and OS improvements can be explained by less treatment intensity, another data point could cast Imfinzi in an unfavorable light in its comparison with Keytruda in cisplatin-ineligible MIBC.
In EV-303, 57% of patients in the Keytruda-Padcev arm (9% in control arm) achieved a pathological complete response with no sign of cancer in resected tissue by central review. In Volga, the number was numerically lower, at 45% for Imfinzi-Padcev (10% in control) by investigator analysis. The pCR endpoint is not affected by postoperative adjuvant treatment, and because the two regimens have the same neoadjuvant treatment intensity, it offers a more direct clue to whether Imfinzi or Keytruda is a better combination partner for Padcev.
Besides the central-versus-local difference, Galbraith suggested there are “subtleties” in these pCR data and again pointed to landmark EFS and OS results in support of Imfinzi.
“The quality of life is good in the post-operative setting with just the Imfinzi maintenance in that setting,” she said. “I think that’s really important because clearly cystectomy is a major procedure, and so to be able to achieve these kinds of landmark EFS and OS levels is really important in the context of a well-tolerated regimen.”
In Volga, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 30% of patients on Imfinzi and Padcev. In EV-303, 45.5% of Keytruda-Padcev recipients experienced grade 3 or higher TRAEs, including two cases (1.2%) leading to death.
Besides the Imfinzi-Padcev doublet, the Volga trial also includes a third arm that adds AZ’s CTLA-4 inhibitor Imjudo in two neoadjuvant cycles and one adjuvant cycle, as the British pharma hopes to differentiate from EV-303.
However, that effort appears to have backfired. The addition of Imjudo, which has a mostly disappointing clinical track record, led to an even smaller EFS advantage, at 39%, over control, with a two-year EFS rate of 60%, which also comes below the doublet’s.
What’s more, unlike the doublet, the triplet arm did not meet statistical significance for OS, as additional follow-up is ongoing.
The Imjudo-containing regimen also appears to work against AZ’s “well-tolerated” pitch, as its rate of grade 3/4 TRAEs jumped to 42%.
Nevertheless, Galbraith is not giving up on the triplet just yet, even though she acknowledged that the “preferred regimen” for most patients will likely be the doublet.
“It’s still possible that some physicians may look at the data and look at individual patients” and choose the triplet, she said, adding that more mature long-term survival data are needed.
Imfinzi, used in combination with chemo, was the first perioperative immunotherapy approved in the U.S. for MIBC, thanks to a 2025 approval in cisplatin-eligible patients. Keytruda-Padcev matched that cisplatin-eligible label in July following a breakthrough cisplatin-ineligible nod based on EV-303 in November 2025. The Keytruda-Padcev regimen has become a star in the bladder cancer field after its impressive first-line metastatic data drew a standing ovation at ESMO 2023.