Drugs Show New Promise in Fighting Advanced Renal Cell Carcinoma

A female nurse and a male doctor, both in white lab coats, talk with a male patient.

Kidney cancer expert Robert Motzer (center) led two clinical trials that showed promising results for patients with advanced renal cell carcinoma.

Two drugs have shown in clinical trials led by Memorial Sloan Kettering medical oncologist and kidney cancer expert Robert J. Motzer that they improve outcomes in patients with advanced renal cell carcinoma (RCC). The drugs, nivolumab (Opdivo®) and cabozantinib, have also both been granted breakthrough status by the US Food and Drug Administration (FDA) for the treatment of advanced RCC. The FDA introduced the breakthrough therapy designation in 2012 to speed the development and review of drugs for serious or life-threatening conditions.

RCC is the most common form of kidney cancer, with more than 330,000 patients diagnosed and more than 140,000 deaths worldwide annually. It’s also particularly aggressive: Approximately 30 percent of patients have metastatic disease at the time of diagnosis — which means the cancer has already spread to other organs — and about one-third of treated patients whose disease is confined to the kidney will relapse.

Renal cell carcinoma is the most common form of kidney cancer.

The current standard of care for metastatic or advanced RCC has been treatment with a drug called everolimus (Afinitor®). Part of a class of drugs known as mTOR inhibitors, it works by slowing the growth and spread of certain cancers and has been used in patients in whom the disease has metastasized or relapsed after treatment with other drugs.

Now, an international, multicenter phase III clinical trial led by Dr. Motzer has shown that nivolumab improves overall survival in previously treated patients with advanced RCC. The trial was published online in the New England Journal of Medicine (NEJM) on September 25 and results were presented at the European Cancer Congress 2015 in Vienna, Austria, on September 26.

This trial has produced practice-changing results.
Robert J. Motzer kidney cancer expert

In the trial, patients with advanced RCC had a median overall survival rate of approximately two years with nivolumab, compared with an overall survival rate of about 19 months with everolimus. The drug works by interfering with a molecular brake known as a PD-1 checkpoint inhibitor that prevents the body’s immune system from attacking tumors.

“Although everolimus and other agents have changed the therapeutic landscape for this disease, the treatments offer only limited overall survival,” says Dr. Motzer. “Renal cell carcinoma is a disease that is crying out for new and novel treatment strategies, and this trial has produced practice-changing results in a cancer that is highly resistant to other therapies.”

An Additional Study, Additional Promise

In another study led in part by Dr. Motzer, cabozantinib improved progression-free survival (PFS) in patients with advanced RCC when compared with everolimus. (PFS is the length of time during and/or after treatment that a patient lives with a disease but it does not get worse.)

The study, published in NEJM on September 26 and also presented at the European Cancer Congress, was a randomized phase II clinical trial in patients with RCC whose disease had progressed despite treatment with at least one VEGFR-targeted therapy.

VEGF — vascular endothelial growth factor — is a signaling protein that stimulates the growth of blood vessels. Solid cancers can’t grow without an adequate blood supply, so the recruitment of blood vessels to a tumor is a key step in tumor growth and spread. Tumors expressing VEGF acquire the ability to grow and metastasize. VEGF-targeted therapies inhibit either VEGF or VEGF receptors (VEGFR).

Cabozantinib — a VEGFR inhibitor— reduced the rate of disease progression or death by 42 percent compared with everolimus. Everolimus was used as a comparison because it’s the standard treatment for patients who have progressed after receiving a VEGFR-targeted therapy. In addition to VEGFR, cabozantinib targets tyrosine kinases MET and AXL, which are believed to be important in RCC, particularly in resistant tumors.

 “Over the past ten years, we have made considerable progress against advanced kidney cancers with the development of targeted drugs in phase III trials led by MSK,” says Dr. Motzer. “The phase III trials of nivolumab and cabozantinib established an improved outcome over standard treatment with everolimus in resistant tumors, and pending regulatory approval will provide two new treatment options. Both of these new drugs will contribute to the progress we’re making against this malignancy.”


Commenting is disabled for this blog post.

Dear Dr. Motzer,

Thanks to you and your research that a patient of yours (me) who was on one of your clinical trials in 2004-2005 with a 4th stage Kidney cancer is up and around - survived! I am cancer free as a direct result of undergoing one of your Clinical trials.
No other words I could say, but a heartfelt "Thank You" for all the good work you and your team is doing!!! God Bless.

Billy Billimoria
A Renal Cell Carcinoma survivor for the past 11 years.

Bill, we’re glad to hear you’re doing well! We forwarded your message to Dr. Motzer.

Hello, my father is suffering from advanced rcc metastasised in lungs as reports and doc says.he is taking sorafenib(nexavar) his health condition is
Becoming poorer slowly. Please suggest any treatment which can do anything better for him.we are from India new Delhi.contact me on my email.

Dear Anuj, we are sorry to hear about your father’s diagnosis. If you are interested in arranging for one of our specialists to provide a medical records review by mail or an in-person visit, please contact our International Center at international@mskcc.org. For more information about our services for international patients, please visit https://www.mskcc.org/experience/become-patient/international-patients. Thank you for reaching out to us.

My husband has RCC stage IV and has now mastitis to his bones. He had one treatment of Opdivo and had an extreme reaction after only one infusion. He has rheumatoid arthritis and Opdivo set off a flair up that caused his knee and hands to swell and become very sensitive and he was hospitalized. First, I wonder why there aren’t any precautions made or questions asked if rheumatoid arthritis can affect Opdivo treatments. Second, is there a possibility that he may have this drug in the future?

Dear Jill, we’re sorry to hear your husband is going through this. We recommend you discuss concerns about side effects and questions about future treatments with his healthcare team. Thank you for your comment, and best wishes to you.

Please provide up to date information about the effectiveness of opdivo for stage 4 rcc. Right kidney was removed and few spots on lung were stable or decreased with votrient but taken off votrient dut to adnopathy soft mass in area where kidney was removed another spot above colon. Please provide information about this drug, side effects, how effective it has been, and any additional information that may be helpful in deciding what is the best treatment for my family member. Thank you

Dear Teresa, for more information about the drug and its side effects, we recommend that you contact the company that makes the drug. You can find the website here: https://www.opdivo.com/

Because every patient is different, we are not able to provide treatment advice on our blog. We recommend that you discuss this with the doctors who are familiar with your family member’s medical history. If you are interested in finding out about having a consultation at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you and your family.