Monday, April 16, 2018
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.”
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.”