This week has brought welcome news to bladder cancer patients and their loved ones. Two drugs with great potential for combatting different types of bladder cancer received different approvals by the U.S. Food and Drug Administration.

At a meeting on December 17, 2019 the Food and Drug Administration (FDA’s) Oncologic Drugs Advisory Committee (ODAC) voted to recommend approval of Merck’s pembrolizumab (Keytruda®) to patients with certain forms of high-risk, non-muscle invasive bladder cancer. [1]

The next day, the FDA granted accelerated approval to a drug developed by Seattle Genetics and Astellas, enfortumab vedotin (Padcev™), to treat adult patients with locally advanced or metastatic urothelial cancer.[2]

These are different types of approvals. Merck’s pembrolizumab is in use for other types of cancer and was approved by a vote of 9 to 4 by ODAC.

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Welcome development
In my role as Chief Executive Officer of the Bladder Cancer Advocacy Network (BCAN), I was present at this very important FDA meeting. The FDA usually follows the recommendation of the advisory committees and this is a welcome development for those with locally advanced or metastatic urothelial cancer.

While the FDA had already approved pembrolizumab for use in bladder cancer, this is a new use of an already approved treatment. Three of four bladder cancer patients are diagnosed with non-muscle invasive disease, when the tumor or tumors have not spread to the muscle layer of the bladder.

For patients for whom Bacille Calmette Guerin or BCG has failed or have persistent or recurrent disease, current treatment protocol dictates that they have their bladders removed during a radical cystectomy, a major surgery and often necessitating removal of other organs and tissues. A radical cystectomy is sometimes not an option for patients who have existing conditions and comorbidities that make major surgery impossible.

Seattle Genetics’ and Astellas’s drug, enfortumab vedotin, was approved under the FDA’s Accelerated Approval Program for locally advanced or metastatic bladder cancer who previously received both platinum-containing chemotherapy and immune checkpoint therapy. It is an exciting development because it is the first drug of its kind with this target.

Enfortumab vedotin is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. It then releases anti-tumor monomeythl auristatin E into the cell, which results in the cell not reproducing and programmed cell death. This treatment is also attractive because it limits the effects on other tissues and allows for higher drug concentrations in the cancer cells.

The FDA approval of enfortumab vedotin is encouraging for patients with locally advanced or metastatic bladder cancer as urothelial cancer appears in nine of ten bladder cancer patients but can also be found in other places in the body. Metastatic urothelial cancer presents few treatment options for patients, and this drug appears to be a significant advance. We hope that this drug is helpful to those who have few options left after other therapies have failed them.

Critical need
While these two drug approvals are good news for the bladder cancer community, they are both good examples of the critical need for continued research to diagnose, treat and monitor bladder cancer.

The “gold standard” for treating non-muscle invasive bladder cancer has been, and in the minds of many, still is BCG, a type of immunotherapy. BCG has been the standard to which all other prospective new treatments must be compared. It is minimally invasive and effective for many who have early stage bladder cancer.

There is currently a critical shortage of BCG. Due to increasing global demand for BCG treatment and as the only source of TICE BCG in many countries, its manufacturer anticipates this shortage to continue throughout 2019 and well into the coming year.

As the voice of U.S. bladder cancer patients, the Bladder Cancer Advocacy Network (BCAN) is deeply concerned and involved with patients, doctors, industry, media, and governmental officials about the current BCG shortage. We understand that BCG is difficult to make and that Merck is operating at 100% capacity to produce BCG, but supply is clearly not meeting demand.

We are deeply grateful to both Astellas/Seattle Genetics and Merck for their commitment to developing new treatment options. Both pembrolizumab and enfortumab vedotin offer new treatment options for patients who desperately need them and may not have viable alternatives.

The Bladder Cancer Advocacy Network welcomes advances in the diagnosis and treatment of bladder cancer like those we saw this week.

On behalf of our community, we want to continue to emphasize the critical need for the FDA to fully explore all viable options for treating and managing this disease. Additional treatment options for bladder cancer are desperately needed.

We can and must do more. Patient lives are at stake!

[1] Highlights of Prescription Information – Pembrolizumab (Keytruda®)[Package Insert]
[2] Highlights of Prescription Information – Enfortumab vedotin (Padcev™) [Package Insert]

This article was first published in Onco’Zine.

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