Imfinzi Combination Shows Efficacy in Bladder Cancer Treatment

In March 2025, the FDA approved neoadjuvant treatment with Imfinzi (durvalumab) plus gemcitabine and cisplatin, followed by single-agent, adjuvant Imfinzi following radical cystectomy in muscle invasive bladder cancer, according to a news release from the United States Food and Drug Administration (FDA).

Notably, the efficacy of the now-FDA-approved approach was evaluated in the randomized, open-label, multicenter, phase 3 NIAGARA trial. In the study, the investigative combination demonstrated a statistically significant improvement in event-free survival and overall survival for patients with muscle invasive bladder cancer who were candidates for radical cystectomy (surgery to remove the urinary bladder).

In an interview with CURE, Dr. Matthew Galsky sat down to discuss the significance of this FDA approval and key takeaways for patients within this population.

“The most important takeaway [message] is that there has been a slow but steady improvement in our ability to treat muscle-invasive bladder cancer,” Galsky explained in the interview. “I think we are at a tipping point in the next few years, where the convergence of better therapies and better technologies — specifically, our ability to measure small amounts of cancer with increased precision using better testing — will all come together and potentially completely change the way we treat bladder cancer moving forward.”

Galsky is professor of Medicine (Hematology and Medical Oncology), director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, and associate director for Translational Research, all located at The Tisch Cancer Institute, the Mount Sinai Health System, in New York, New York.

CURE: To begin, what makes this approval significant for patients and providers managing muscle-invasive bladder cancer?

Galsky: A standard treatment for muscle-invasive bladder cancer is the surgical removal of the bladder. We know that after the bladder is removed, a subset of individuals will experience the cancer reappearing elsewhere in the body, developing metastatic recurrence, typically months to years later.

For decades, doctors attempted to combine chemotherapy with surgery to eradicate any microscopic cancer cells that might be present, aiming to reduce the risk of metastatic recurrence. When chemotherapy is administered before surgery, it's called neoadjuvant therapy. This concept of giving chemotherapy prior to surgery to treat potential microscopic spread of cancer is used in various solid tumors. When chemotherapy is given after surgery, it's known as adjuvant therapy.

For decades, the only neoadjuvant therapy proved beneficial in muscle-invasive bladder cancer was a combination of chemotherapy drugs, including cisplatin. This truly represented the standard treatment approach for many years because nothing had been shown to be superior.

Finally, after several decades, the NIAGARA trial demonstrated that integrating immunotherapy in the pre-surgical and post-surgical periods decreases the risk of metastatic disease development and improves longevity for patients.

The NIAGARA trial demonstrated a 32% reduction in the risk of recurrence and a 25% reduction in the risk of death. How do these results compare with historical outcomes using neoadjuvant chemotherapy alone?

The historical outcomes for patients with muscle-invasive bladder cancer treated with chemotherapy followed by surgery are really mirrored by the control arm of this study, as that was the control arm. Now, patients in this study fared slightly better than what we typically observe historically, likely because our treatment and supportive care have evolved.

However, we know that beyond that standard of care, the addition of immune checkpoint blockade, or Tecentriq (atezolizumab) — both in the pre-surgical and post-surgical periods — improves our ability to prevent cancer recurrence and allows patients to live longer, even exceeding what we consider the contemporary and historical standard treatment.

What can patients expect during treatment with this combination of immunotherapy and chemotherapy — both in terms of the timeline and potential side effects?

Immune checkpoint blockade involves drugs that we call PD-1 or PDL-1 inhibitors, and Imfinzi is a PDL-1 inhibitor. These drugs have been used alone in various indications and also combined with chemotherapy for a variety of different indications across various solid tumors. So, oncologists are quite accustomed to administering these combinations at this point.

Our extensive experience thus far indicates that when you give immunotherapy with chemotherapy, it does not seem to worsen the side effects of the chemotherapy, nor does the chemotherapy seem to worsen the side effects of the immunotherapy. That said, when you administer two classes of drugs simultaneously, there's a higher overall risk for side effects because you have the potential side effects of each component, but they don't amplify each other.

Regarding side effects, those that can occur with cisplatin-based chemotherapy, in particular, are the ones many people associate with chemotherapy. These can include fatigue, nausea, vomiting, hair loss, an impact on kidney function and neuropathy, such as numbness and tingling in the fingers and toes. Fortunately, many of these side effects are transient and reversible with chemotherapy. Immune checkpoint blockade, or immunotherapy, has a very different side effect profile; many patients experience few to no side effects with it. However, a subset of patients will develop side effects that we refer to as immune-related [side effects].

These involve inflammation of different parts of the body and really mimic what we think of as autoimmune diseases, except usually, when these side effects occur, they affect one organ in an individual rather than multiple organs. For example, one individual might develop inflammation of the skin, called dermatitis, which manifests as a rash or itching. Another person might get inflammation of the bowel, called colitis, which manifests as diarrhea. When these side effects occur, if they're mild, immunotherapy is held. If they're more severe, they are typically treated with steroid medication.

When we give chemotherapy with immunotherapy prior to surgery, in the neoadjuvant setting, it's administered in three-week cycles. During each three-week cycle, treatment is given twice, once in the first week and once in the second week. These three-week cycles are repeated four times, and then surgery is performed. After surgery, the immunotherapy is generally given once a month to complete eight more months of treatment.

What follow-up research or real-world data are needed to further validate the role of this regimen?

There are several other trials testing a similar concept: should we integrate immune checkpoint blockade with cisplatin-based chemotherapy in the perioperative setting, meaning both before and after surgery?

The results of these trials collectively will, of course, enhance our understanding of the full context regarding what is being achieved with these regimens. However, as a standalone trial, NIAGARA led to FDA approval of this regimen and is now an accepted standard of care for use in patients with muscle-invasive bladder cancer.

Transcript has been edited for clarity and conciseness.

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