Immunotherapy Combination Offers a Better Chance at Longer Survival for Patients with Metastatic Kidney Cancer

MSK medical oncologist Robert Motzer

Medical oncologist Robert Motzer led a clinical trial comparing the combination of two immunotherapies with the standard of care for patients with a type of kidney cancer.

Update: On April 16, 2018, the FDA approved the combination of nivolumab and ipilimumab for the treatment of people with poor- and intermediate-risk advanced renal cell carcinoma.

On March 21, 2018, new data from this study were published in the New England Journal of Medicine, further proving the efficacy of the ipilimumab and nivolumab combination. The trial included 1,096 total patients with metastatic renal cell carcinoma, and researchers found that overall survival favored the immunotherapy combination, with an 18-month overall survival rate of 78% compared with 68% with sunitinib alone.

Original post: For years, oncologists had very few choices to treat patients with metastatic renal cell carcinoma. Their primary options were two types of immunotherapy drugs, interferon-alpha and interleukin-2, then the targeted therapy sunitinib (Sutent®), which was approved in 2006. Since then, sunitinib has remained the standard of care as initial treatment for this disease.

People with metastatic renal cell carcinoma may soon have a new option to treat their disease and extend their life.

On September 7, 2017, Bristol-Myers Squibb announced that the combination of the immunotherapies ipilimumab (Yervoy®) and nivolumab (Opdivo®) extended survival for people with metastatic renal cell carcinoma in a phase III trial. The study, led by MSK medical oncologist Robert Motzer, compared the combination of those immunotherapies against sunitinib alone in patients with the disease who had not yet received treatment.

At the European Society for Medical Oncology (ESMO) Congress on September 10, 2017, oncologist Bernard Escudier of the Institut Gustave Roussy in France reported that the median overall survival for patients treated with sunitinib was 26.0 months while the median overall survival for those treated with the immunotherapy combination was not yet reached. Dr. Escudier was also an investigator on the study.

“We have seen a significant improvement in overall survival,” Dr. Motzer said in an interview, with a caveat. “The data must continue to be looked at carefully to determine which patients will do better with ipilimumab and nivolumab and which might do better with sunitinib.”

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He said that there was a clear benefit for the combination among people with poor- and intermediate-risk renal cell carcinoma in extending overall survival and reducing tumor size. However, a small group of patients with favorable risk did see a higher rate of tumor shrinkage with sunitinib.

Dr. Motzer highlighted the fact that the immunotherapy combination works completely differently from sunitinib and provides a better chance for longer survival for patients who have not yet been treated — what is known as first-line therapy, a crucial area of unmet need.

“It’s a completely different mechanism of action and it introduces a new type of therapy in this setting,” Dr. Motzer says. “And with the exception of one trial many years back, we haven’t been able to demonstrate survival benefit in first-line therapy for renal cell carcinoma.”

Because the drugs work differently, the side effects are different too, said Dr. Motzer. The possible side effects seen with immunotherapies are inflammation of the lungs as well as the bowel, which can lead to diarrhea; skin rashes; and more.

“At MSK, we have extensive experience in treating patients with immunotherapies — with kidney cancer, melanoma, and beyond — and handling immune-related side effects,” he said.

Dr. Motzer found it important to consider the larger context of this one trial.

“This combination was initially developed here at MSK by [cancer immunologist] Jedd Wolchok in melanoma and it’s now the standard of care in that disease,” he said. “We’re following the same path in kidney cancer now.”

The phase III study of ipilimumb and nivolumab was supported by Bristol-Myers Squibb, the manufacturer of the two drugs.


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i do understand that the purpose of this phase 3 trial was to compare combined immunotherapy against sunitinib. here's what i don't understand: why not a three-drug cocktail and sunitinib (it seems to work better with some people) and also include the two immunotherapy drugs used in your trial?

Dear Alan, we sent your question to Dr. Motzer, who explained that sunitinib has been combined with nivolumab, and the combination was felt to have too many side effects. Therefore, combining these three drugs is not recommended, nor is it under study in clinical trials. Thank you for your comment, and best wishes to you.

With metastatic HLRCC, would this combination be an option at some point if disease progresses? Diagnosed 3 1/2 years ago , have been on Opdivo in the past.

Does ipi-divo immunotherapy work on metastatic papillary renal cell carcinoma? If it does, what might be life expectancy?

I was diagnosed with stage 4 RCC in January 2018. I had numerous nodules, lesions, tumors in both lungs and a tumor on my kidney about 7cm x 10 cm. I started on Cabozantinib in February 2018 and it worked for 3 months and then stopped working. I was put on Yervoy/Opdivo como on August 20th 2018. I have not had scans again, but my persistent cough went away, my skin color returned, put on 12 lbs and my blood work in every aspect (live, kidney enzymes, white blood cells, etc.) are perfect. I am 61 years of age and in great health (other than cancer). I have not had surgery on kidney tumor. What would be my prognosis? Doctors won't tell me how long I have. Months? Years? This is the best I have felt in 3 years! So I know something is working. Should I have surgery to remove tumor?

Dear Adam, we’re sorry to hear about your diagnosis, but glad to hear that you’re feeling well at this time. We are not able to answer questions about prognosis or provide treatment advice on our blog. If you’re interested in coming to MSK for a consultation or second opinion, you can call 800-525-2225 or go to for more information. Thank you for your comment, and best wishes to you.

I was diagnosed with Stage 4 Renal Cell Carcinoma on March 19th of 2018.
I have been thru 8 months of treatment with Sutent which worked for about 8 months before my tumor started growing again. I am starting Opdivo and Yervoy in several days. I have many questions about this treatment. Is this treatment better than Proton Beam Therapy?? I would love to talk to someone about the decisions I need to make for my care.
Thank you