New Trial Data Signals Big Step Forward For Cisplatin‑Ineligible Bladder Cancer Patients

Early results from the Phase 3 VOLGA trial show that patients with muscle‑invasive bladder cancer (MIBC) who received perioperative durvalumab plus neoadjuvant enfortumab vedotin (EV) experienced statistically significant and clinically meaningful improvements in both event‑free survival and overall survival compared to those treated with the current standard of care.

AstraZeneca, which manufactures durvalumab (Imfinzi), announced the promising findings in May 2026, noting the potential impact of pairing durvalumab with EV for patients with MIBC, particularly those who cannot receive cisplatin.

Dr. David Aggen, a medical oncologist at Memorial Sloan Kettering Cancer Center, called the early data “a potentially meaningful advance for cisplatin‑ineligible patients.”

He emphasized that VOLGA reinforces the activity of EV when combined with a different checkpoint inhibitor, durvalumab, an anti‑PD‑L1 antibody.

Dr. Alexandra Drakaki, a hematologist at UCLA and a leading investigator involved in presenting the VOLGA trial findings, says the results have the potential to change practice.

“Today, we can say with confidence that durvalumab and enfortumab vedotin with or without tremelimumab in the perioperative setting do improve the event free survival, while durvalumab with enfortumab vedotin can also improve overall survival,” Dr. Drakaki tells SurvivorNet Connect.

Dr. Aggen cautions that the full dataset, including Kaplan‑Meier curves, pathologic complete response rates, and mature survival outcomes, is needed to fully understand the magnitude of benefit.

He notes that adding CTLA‑4 inhibitors in other trials has increased autoimmune toxicity, making the event‑free survival benefit in VOLGA an important factor to watch.

“The lack of a mature OS does not close the door on dual checkpoint blockade, but does beg the question as to whether an ADC plus PD-(L)1 regimen is the sweet spot for most patients,” Dr. Aggen says.

A Chemo-Free Option Post-Surgery

Dr. Drakaki explains that the EV303 trial and the VOLGA trial are “two distinct trials,” even if they studied the same patient population.

“The EV303 trial design included adjuvant enfortumab vedotin along with pembrolizumab, while in the VOLGA trial, only adjuvant durvalumab was given after surgery. Therefore, having a chemotherapy-free regimen after surgery is more appealing and preferred by patients,” Dr. Drakaki said.

Seeing the full dataset will help clarify how much benefit comes from the neoadjuvant versus adjuvant components and how the combination of EV and durvalumab performs across the perioperative setting.

“The big story is that EV plus a PD‑(L)1 inhibitor is emerging as the perioperative backbone for cisplatin‑ineligible MIBC,” Dr. Aggen says. “We’re entering a new era where, with more active regimens, we need trials that determine whether bladder‑sparing approaches can maintain cure rates.”

AstraZeneca notes that up to 50% of patients are ineligible for cisplatin due to kidney function or other comorbidities. Historically, these patients have relied on radical cystectomy alone; however, recurrence rates remain high, and outcomes are poor.

Despite the encouraging signals, Dr. Aggen stresses that more data are needed before clinicians can confidently position this regimen against the current standard of care.

Dr. Drakaki believes durvalumab paired with EV for patients with MIBC has the potential to be “practice-changing.” However, the full dataset will help determine its influence on the current standard of care once it is fully released.