FDA Approves New Combination Therapy for Kidney Cancer

Kidneys_GU Blog_FBOn May 13, the Food and Drug Administration (FDA) approved a new oral combination therapy for patients with advanced renal cell carcinoma (RCC), the most common kidney cancer in adults.

This combination therapy involves taking capsules of lenvatinib and everolimus on a daily basis. Both drugs are signal transduction inhibitors that stop some of the signals within cells that make them grow and divide. Lenvatinib (brand name Lenvima) works by inhibiting vascular endothelial growth factor (VEGF) receptors, halting blood vessel formation (angiogenesis) and fibroblast growth factor (FGF) receptors. FGF receptors are thought to be responsible for the development of cancer progression (treatment-resistance) following other anti-VEGF therapies. Levantinib was first FDA-approved in 2015 to treat some forms of recurrent and metastatic thyroid cancer. Everolimus stops a particular protein called mTOR from working which helps stop cancer growth. Everolimus was the first mTOR inhibitor approved in 2009 for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

This treatment regimen is only FDA-approved as a second-line treatment for those who have already undergone one prior anti-angiogenic therapy. Common anti-angiogenic therapies for metastatic kidney cancer include sunitinib and pazopanib. Rather than targeting the tumor cells directly, anti-angiogenic therapies aim to prevent the growth of blood vessels the tumors depend on for survival.

Dr. Ana Molina of the Weill Cornell Medicine Genitourinary Oncology team led the initial study that tested this combined treatment which demonstrated that the regimen was not only safe, but showed impressive enough anti-cancer activity to warrant a larger, multi-center, randomized trial.

In the randomized trial that ultimately led to FDA-approval, patients who received lenvatinib and everolimus had significant improvement in progression-free survival (PFS) of 14.6 months versus 5.5 months with only everolimus. The overall response rate was 43% with the combination, compared with 27% with Lenvatinib alone and 6% with everolimus. The median overall survival was 25.5 months for the combination arm, 19.1 months in the Lenvatinib monotherapy arm and 15.4 months in the everolimus arm. Side effects included diarrhea, fatigue, high blood pressure (hypertension), nausea and vomiting, weight loss and protein in the urine.

We continue to offer lenvatinib and everolimus as combination therapy and encourage you to ask about whether it would a good treatment course for you.

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.