New Metastatic Bladder Cancer Therapy Approved by FDA: Enfortumab Vedotin (Padcev)

MSK medical oncologist and bladder cancer specialist Jonathan Rosenberg

Dr. Jonathan Rosenberg says the new approval of enfortumab vedotin as a first-line therapy for urothelial carcinoma “feels like a huge sea change in how we treat patients, and hopefully a turning point toward longer survival in this difficult disease.”

A powerful treatment is now an option for some people with metastatic bladder cancer, the fifth most common form of cancer.

The U.S. Food and Drug Administration (FDA) on April 3 approved enfortumab vedotin (Padcev®) plus the immunotherapy drug pembrolizumab (Keytruda®) for people newly diagnosed with metastatic urothelial carcinoma — a cancer that primarily arises in the bladder and also occurs in other parts of the urinary system.

This therapy shrank tumors in two-thirds of patients in a recent clinical trial, and 12% saw their cancers completely disappear.

New Approval for Metastatic Bladder Cancer To Have Major Impact

The FDA’s new approval greatly expands the number of people with bladder cancer who could benefit from the drug. Doctors can now use enfortumab vedotin as a first-line treatment for metastatic bladder cancer in people who cannot receive cisplatin-based chemotherapy, the standard first-line treatment. About half of all patients with metastatic bladder cancer are not able to receive cisplatin-based chemotherapy.

“This approval as a first-line treatment will have a major impact in treating metastatic bladder cancer,” says Memorial Sloan Kettering Cancer Center (MSK) genitourinary oncologist and bladder cancer specialist Jonathan Rosenberg, MD. Dr. Rosenberg has led multiple clinical trials (research studies) testing enfortumab vedotin alone or in combination with other drugs in bladder cancer.

“We can give enfortumab vedotin right away in combination with pembrolizumab instead of having people go through other treatments that don’t work. Eventually, depending on results of other ongoing trials, it could replace chemotherapy as a standard of care in most patients, even those eligible for cisplatin.”

Enfortumab vedotin was previously approved in 2019 for a more limited patient group — those who cannot have surgery and whose disease persists despite prior treatment with immunotherapy, chemotherapy, or both.

Antibody-Drug Conjugates Deliver a Precise Payload to Cancer Cells

Enfortumab vedotin is a new type of therapy called an antibody-drug conjugate. This type of drug works to treat cancer by combining three parts:

  • An antibody that binds to specific proteins or receptors on the surface of the cancer cell.
  • A drug, such as chemotherapy, that is toxic to the cancer cell.
  • A linker that connects the drug and antibody, keeping the drug bound to the antibody and shielded from the body until it arrives at the cancer cell.

Targeting the Nectin-4 Protein in Bladder Cancer

On a search-and-destroy mission, enfortumab vedotin binds to a protein on cancer cells called nectin-4 and delivers a chemotherapy drug called monomethyl auristatin E. The antibody-drug conjugate selectively delivers monomethyl auristatin E to the cancer cells, killing them while sparing normal body parts from high doses of the drug.

Woman sitting in chair

Oka Carroll says the weekly infusions with enfortumab vedotin — some of which she was able to receive at MSK Nassau, only 10 miles from her home in Great Neck — were easier to manage than the chemotherapy had been.

Enfortumab Vedotin Results: Tumors Shrink in Most Patients With Metastatic Urothelial Carcinoma

In the clinical trial, enfortumab vedotin was given along with the checkpoint inhibitor pembrolizumab (Keytruda®). Researchers tested this combination approach in people newly diagnosed with metastatic urothelial cancer who were unable to receive cisplatin chemotherapy.

The combination approach shrank tumors in 68% of patients, which appears much better than standard chemotherapy treatments such as gemcitabine and carboplatin. In addition, 12% of patients had their tumors disappear completely on imaging tests.

Metastatic Bladder Cancer Survival Story With Enfortumab Vedotin

In early 2020, Oka Carroll was diagnosed at age 66 with urothelial carcinoma of the renal pelvis — the part of the kidney that “catches” the urine from the kidney. In her case, the cancer did not affect the bladder itself, but Dr. Rosenberg explains that from a treatment standpoint, “it’s the same illness” as bladder cancer.

After doctors on Long Island removed Oka’s right kidney and some lymph nodes, she came to MSK for follow-up treatment. Dr. Rosenberg gave her chemotherapy and immunotherapy. But by the end of the year, scans showed that the cancer was growing in several remaining lymph nodes. In the past, Oka would have been out of options. But Dr. Rosenberg suggested enfortumab vedotin, newly approved for patients in her situation.

“He recommended it and we trust his judgment completely — he’s always planning ahead for the next step,” Oka says.

Oka started treatment with enfortumab vedotin in December 2020 and had a good response right away. Over the next year, CT scans every three months showed that the cancer had stopped in its tracks. Oka says the weekly infusions with enfortumab vedotin — some of which she was able to receive at MSK Nassau, only 10 miles from her home in Great Neck — were easier to manage than the chemotherapy had been.

The biggest side effect was neuropathy — tingling and numbness — in her feet, which gradually impaired her ability to walk. After a year, Dr. Rosenberg suggested Oka take a break from the drug while they continued to monitor the lymph nodes. Fifteen months after she stopped treatment, her disease remains stable, with no progression. Physical therapy with MSK physiatrist Christian M. Custodio, MD, has greatly helped with the neuropathy.

Enfortumab Vedotin Eliminates Lung Cancer Metastases in Patient

Ester Bardror was also diagnosed with urothelial carcinoma, at age 64. She came to MSK in 2019 after noticing blood in the urine. MSK urologic surgeon Jonathan Coleman, MD, removed her kidney because the cancer had started in the renal pelvis. Ester hoped she wouldn’t need more treatment, but scans soon showed the cancer had spread to her lungs.

She began treatment with chemotherapy and immunotherapy under the care of MSK genitourinary oncologist and bladder cancer specialist Dean Bajorin, MD. These drugs didn’t work. So in 2021, she began receiving enfortumab vedotin in weekly infusions at MSK’s Rockefeller Outpatient Pavilion in midtown Manhattan. After just a few months, there was no visible cancer in the lungs. MSK doctors continue to monitor her closely with regular scans.

Grandmother and grandfather on couch with grandson

Ester Bardror, with husband Itzhak and grandson Benjamin, enjoys spending time with family in Brooklyn. Her cancer, which had spread to her lungs, responded well to enfortumab vedotin.

“I’m really happy with how I’m doing now,” Ester says. “I had no serious side effects, just a little numbness in the toes.” Ester and her husband live near her daughter in Brooklyn and enjoy spending time with her and several grandkids.

“As an oncologist treating these patients for two decades, this feels like a huge sea change in how we treat patients, and hopefully a turning point toward longer survival in this difficult disease,” Dr. Rosenberg says.


Click to learn about professional relationships and financial interests of Dr. Rosenberg and Dr. Bajorin.