FDA Approves Atezolizumab For Bladder Cancer Immunotherapy


A game changing new immunotherapy drug, atezolizumab, has won FDA approval for treatment of patients with metastatic urothelial carcinoma, a type of bladder cancer.

The drug is the first new treatment for this form of the disease in more than 20 years, and is expected to have a major impact on bladder cancer, the fifth most common form of cancer and the fourth most common in men. Its benefit appears to be lasting in some patients.

Individuals diagnosed with advanced bladder cancer have not traditionally had effective treatment options. Although chemotherapy can temporarily hold the disease at bay, it often comes back within months.

Now, the US FDA has approved atezolizumab (Tencentriq) for patients with metastatic urothelial carcinoma. The drug’s approval stemmed largely from results of a phase II clinical trial led by Memorial Sloan Kettering medical oncologist Jonathan Rosenberg.

“We’re seeing people get lasting responses with atezolizumab after chemotherapy has stopped working. That’s a game-changer for these patients, and it represents a huge breakthrough,"

says Dr. Rosenberg.

Benefits of Atezolizumab

Results from the clinical trial showed that atezolizumab shrank tumors in a significant portion of patients. The benefit appeared to be lasting in many people. Among patients in the trial who had anticancer responses, 84 percent were still responding after about one year.

Although the approval is for use in certain bladder cancer patients only, those with metastatic disease who previously have received chemotherapy, Dr. Rosenberg says this approval might later expand to others with the disease.

“These patients have few options and the existing treatments that are available are very toxic—and none of them are known to prolong life,” he says.

Atezolizumab is one of a new group of immunotherapy drugs called checkpoint inhibitors. These drugs take the brakes off the immune system, allowing it to attack the cancer.

The braking molecule targeted by atezolizumab is called PD-L1, which is expressed on the surface of some cancer cells and immune cells and prevents the immune system from recognizing that the cancer cells pose a threat. Other checkpoint inhibitors have already been approved for the treatment of several other cancers, including melanoma, lung, and kidney cancers.

Complete Remission

For Craig Brown, who participated in the clinical trial, atezolizumab has been nothing short of a miracle.

In early 2014, he was diagnosed with stage IV bladder cancer that had spread to his ribs. He began receiving platinum-based chemotherapy (the most common type) once a week for nearly six months, but the treatment proved to have limited benefit and brought severe side effects.

“The chemo made me extremely tired, and it took a while to wear off,” he says. “At some points I could barely get out of bed after receiving it. There was some improvement with the cancer, but not complete remission, and as soon as I stopped taking the chemo, it came back almost immediately."

MSK medical oncologist Dean Bajorin enrolled Mr. Brown in the atezolizumab trial in October 2014. Mr. Brown says the change to his health was immediate and dramatic.

Not only did the new drug begin shrinking the cancer immediately, it also has caused no noticeable side effects during the 19 months he has been on it. He is still receiving atezolizumab once every three weeks under the care of Dr. Bajorin.

“It’s been tremendous,” he says. “I’m a CPA, and I’ve been able to work from early in the morning to late at night six days a week like I did before the cancer. The doctors tell me I’m in complete remission. It puts a whole new spin on your life to be this fortunate."

Lasting Potency

Atezolizumab is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein Programmed cell death-ligand 1. It is currently on clinical trials for colorectal cancer, melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma.

Atezolizumab blocks the interaction of PD-L1 with PD-1 and B7.1. PD-L1 can be highly expressed on certain tumors, which is thought to lead to reduced activation of immune cells (cytotoxic T-cells in particular) that might otherwise recognize and attack the cancer.

Dr. Rosenberg says that the most impressive benefit of atezolizumab may be its lasting effectiveness.

“That is not something we have seen before with bladder cancer,” he explains. “There are some patients whose cancer disappeared completely, even after spreading to other sites. You never saw that on a regular basis with chemotherapy-resistant bladder cancer."

He says upcoming clinical trials will test atezolizumab in additional bladder cancer patients, either alone or in combination with chemotherapy, angiogenesis inhibitors, or other targeted agents.

There also is a great deal of interest in seeing whether atezolizumab can be an effective and safe treatment earlier in the disease process.

Jonathan E Rosenberg et al.
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial
The Lancet (2016). DOI: 10.1016/S0140-6736(16)00561-4