Category: Bladder Cancer

Immunotherapies for Advanced Bladder Cancers

Cancer MicroscopeImmunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types of bladder cancer immunotherapies currently available:

1. Atezolizumab (brand name Tecentriq) is an FDA-approved immunotherapy for urothelial carcinoma, the most common form of bladder cancer. Atezolizumab is an immune checkpoint blockade or “checkpoint inhibitor.” It selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it. It had been more than two decades since the FDA approved a new bladder cancer treatment.

Atezolizumab is only approved for urothelial carcinoma that has grown or recurred after previous chemotherapy, and we offer this treatment at Weill Cornell Medicine. We are also currently testing another PD-L1 checkpoint inhibitor alone or in combination with another immune checkpoint antibody versus standard chemotherapy through an open phase III clinical trial.

2. Ramucirumab is a monoclonal antibody that binds to the Vascular Endothelial Growth Factor (VEGF) receptor-2. This is a receptor found predominantly on blood vessels. Angiogenesis is a process where vessels grow to feed tumors and blocking this pathway can be helpful at stopping the growth of these vessels, particularly in combination with chemotherapy. We previously completed a randomized phase III trial which demonstrated that patients who got docetaxel (Taxotere) chemotherapy plus ramicurimab had more than twice the tumor shrinkage and double the time until tumor growth compared to docetaxel chemo alone; This study was recently published in the Journal of Clinical Oncology. Based upon our results, we recently opened a phase III trial using this drug in combination with chemotherapy. People who have already received chemotherapy, and those who have received chemo followed by atezolizumab or other checkpoint inhibitors are eligible for this clinical trial.

3. IMMU-132 (also known as Sacituzumab Govitecan) is an antibody drug conjugate that leverages the capability of monoclonal antibodies to attach to specific targets on cancer cells. By attaching a drug to the monoclonal antibodies, treatments are able to “hitch a ride” into the cancer cells.

This treatment is a potential good treatment fit for adults with metastatic bladder cancers who have not responded to chemotherapy or who have relapsed after chemotherapy or PL-1/PD-L1 checkpoint inhibitor immune treatment.

Initial positive results in the phase I trial led to a phase II clinical trial that is currently open to enrollment. Learn more about how this drug works in the body and get more information about our open IMMU-132 clinical trial by checking out our recent blog post, “Doing Better on Behalf of Bladder Cancer Patients.”

4. REGN2810 is a monoclonal antibody – a type of protein that works by blocking the programmed death receptor 1 (PD-1), a cell receptor on immune cells that is involved in preventing the immune cells from destroying other cells. Through our open clinical trial, patients with bladder and other urothelial cancers who have received prior treatment with checkpoint inhibitors (such as atezolizumab) can get the combination of the REGN2810 drug with immune boosters.

Matters of the Bladder: 9 Facts about Bladder Cancer

Bladder_ImageThe bladder is an organ comprised of several layers of cells, and its main job is to store urine. When it’s full, it lets you know. But, chances are there are many other things about the bladder that you may not know. In honor of bladder cancer awareness month in May, here are 9 facts:

  1. There are different types of bladder cancer. Tumors typically form within the different cell layers of the bladder. The name of the specific type of bladder cancer refers to where the cancer started. That’s why bladder cancer is sometimes referred to as urothelial (one of the layers) carcinoma (a fancy word for cancer).
  2. Blood in the urine is a red flag. The most common sign of bladder cancer is blood in the urine (also called hematuria) that can be seen by the naked eye. Usually it is painless. But, bladder cancer isn’t the only culprit for blood in the urine. It can also be caused by an infection or kidney stones. Blood in the urine requires evaluation by a healthcare professional.
  3. It’s common. Bladder cancer is the fifth most commonly diagnosed cancer in the U.S. The National Cancer Institute (NCI) estimates 76,960 new cases of bladder cancer and 16,390 deaths from the disease in 2016.
  4. But lacks funding for research. It is through research that we are able to develop new treatments and ultimately cures. Despite being the fifth most commonly diagnosed cancer in the U.S., bladder cancer ranks 23rd in terms of federal funding.
  5. Some people are at increased risk. Smoking is the greatest risk factor. The good news is you can reduce your risk if you quit. We even have a program to help you get started. Bladder cancer is 3x more common in men than in women, and Caucasians are 2x as likely to develop bladder cancer than African Americans or Hispanics. Risk also increases as you get older and if you have a family history. Visit the Bladder Cancer Advocacy Network to learn more about additional risk factors.
  6. It is diagnosed through different tests. These typically include imaging tests such as ultrasounds, MRIs or CT scans to better see your bladder, urine testing to determine the presence of cancer cells and a biopsy to remove a sample if an area contains cells that appear suspicious.
  7. Treatment will depend on the type of bladder cancer and how advanced and aggressive it is. Treatments vary by stage and include surgery, chemotherapy and immunotherapy.
  8. Immunotherapy offers promise. Immunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types currently in clinical trials and the FDA just approved a new treatment called atezolizumab (brand name: Tecentriq). Our team recently presented and published our findings on another form of immunotherapy for bladder cancer, an antibody drug conjugate called IMMU-132.
  9. We are dedicated to and on the forefront of bladder cancer research. At Weill Cornell Medicine, we are committed to research in order to improve outcomes for patients with this disease. The newest member of our Genitourinary Oncology team, Dr. Bishoy Faltas, is dedicated to understanding the genetic makeup of bladder cancer. He’s currently focusing on the genomic changes that happen as the tumors become resistant to chemotherapy. We’re also trying to understand why some patients respond well to immunotherapy, while others do not.

FDA Approves New Immunotherapy for Bladder Cancer

Cancer LabFor the first time in more than 20 years, today the FDA granted approval to a new treatment for urothelial carcinoma, the most common form of bladder cancer.

Tecentriq, also known as atezolizumab, is an immune checkpoint blockade or inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface. This is the first PD-L1 inhibitor that has been approved by the FDA for any disease.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it, but PD-L1 inhibitors help the body to “see” the cancer and use the immune system to fight it.

This treatment has shown promise for platinum-resistant metastatic urothelial carcinoma – an advanced cancer that does not respond to traditional chemotherapies and which so far has very few other effective therapies.

In the study that ultimately led to atezolizumab’s approval by the FDA, it was shown to be effective at helping unleash the power of the immune system to recognize and attack these tumor cells.

The patients who responded positively to this treatment can do well on it for a long time. This is sometimes referred to as having a “durable response.” Few side effects were seen with this drug and they were mild. Severe side effects were rare and tied to too much immune activity. These study results first led to the FDA granting atezolizumab priority review designation in March 2016 to put it on the fast track for full FDA approval.

Additionally, in this study the investigators identified a correlation between mutational load and response to the drug. This means that when there was a higher concentration of proteins that could be recognized by the body, there was more sensitivity to this immunotherapy.

At Weill Cornell Medicine, we have been involved in the development of several types of immunotherapy and are at the forefront of developing ways to better determine which patients are most likely to respond to treatment. We are conducting research on how mutations and the “mutational load” can lead to the formation of neoantigens and the impact these neoantigens have on immunotherapy response in order to identify the patients most likely to benefit from this therapy.

We’re very excited to be able to offer Tecentriq/atezolizumab to our patients and encourage you to inquire about whether it’s a good fit for you. Additionally, we continue our research with immunotherapy and monoclonal antibodies for patients with urothelial cancer. One open clinical trial is testing whether a single checkpoint inhibitor (targeted at PD-L1) or dual checkpoint inhibitor (targeted at both PD-L1 and CTLA4 – a protein on the T-cell) is more effective against tumors compared with chemotherapy.