FDA Approves Nivolumab and Ipilimumab Combination for Advanced Kidney Cancer

The Food and Drug Administration (FDA) approved the immunotherapy drugs Opdivo and Yervoy in combination as an initial, or first-line, treatment for patients with advanced kidney cancer whose disease has an intermediate or poor prognosis.

This is the first immunotherapy regimen to be approved by FDA for the initial treatment of patients with kidney cancer. Nivolumab was previously approved to treat patients with advanced kidney cancer whose disease had gotten worse after treatment with standard first-line therapy.

The new approval was based on results from an international phase 3 clinical trial. In the trial, people with intermediate- or poor-risk advanced kidney cancer treated with the combination experienced improved survival compared with Sutent, the current standard treatment. and Results from the trial, which was funded by Bristol-Myers Squibb and Ono Pharmaceutical, were reported April 5 in the New England Journal of Medicine (NEJM).

Better Outcomes with Immunotherapy

The trial, called CheckMate 214, involved nearly 1,100 patients with previously untreated advanced renal cell carcinoma (RCC), which is the most common type of kidney cancer. (For this study, advanced RCC was defined as cancer that was not amenable to potentially curative surgery radiation therapy or that had spread to other areas of the body.)

The majority of patients in each treatment group had intermediate- or poor-risk disease. Oncologists use well-established risk factors to categorize patients with advanced kidney cancer into favorable-, intermediate-, and poor-risk groups. Approximately 75% of all patients with advanced kidney cancer have intermediate- or poor-risk disease.

At 18 months after initiating treatment, 75% of patients treated with the immunotherapy combination were still alive, compared with 60% of those treated with sunitinib. At a median follow-up of 25 months, the median overall survival for patients treated with the immunotherapy combination had not been reached. For patients treated with sunitinib, it was 26 months.

More patients assigned to the immunotherapy combination than to sunitinib experienced an objective tumor response (42% versus 27%), including complete responses  (9% versus 1%), meaning their cancer was no longer detectable.

Fewer patients in the trial treated with nivolumab and ipilimumab than with sunitinib experienced serious side effects (46% versus 63%). However, more patients in the immunotherapy group discontinued treatment because of side effects (22% versus 12%). There were eight deaths likely related to treatment among patients treated with nivolumab and ipilimumab, the trial researchers reported, and four among patients treated with sunitinib.

Despite the prevalence of side effects and greater percentage of patients stopping treatment, patients who received the immunotherapy combination reported higher quality of life throughout the study.

Patients with Favorable-Risk Disease Fared Better with Sunitinib

The improvements in survival and tumor response rates seen in patients with intermediate- and poor-risk disease treated with the immunotherapy combination were not seen in patients with favorable-risk disease.

The study authors acknowledged the different outcomes for patients with favorable-risk disease but said that the results should be “interpreted with caution because of the exploratory nature of the analysis, the small subgroup sample, and the immaturity of survival data.” However, they continued, the disparate results “highlight the need to better understand the underlying biologic processes driving responses to these two different treatment regimens.”

Moving Beyond Blocking the Tumor Blood Supply

Since 2005, FDA has approved numerous drugs like sunitinib that target angiogenesis, the growth of new blood vessels that nourish tumors, to treat kidney cancer. Unlike antiangiogenesis drugs, nivolumab and ipilimumab work by blocking proteins that deter or dampen an immune response against tumors.

The new approval will likely change how patients are treated, said Dr. Jonasch. Now, patients with intermediate- or poor-risk disease likely will receive nivolumab and ipilimumab as their initial treatment, he suggested.



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