FDA News

FDA approves Opdivo-Yervoy combination for renal cell carcinoma

The FDA today approved the combination of nivolumab and ipilimumab for the treatment of intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma.

The FDA based this decision on data from 847 intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma from the randomized open-label CheckMate-214 trial, which compared the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) with sunitinib (Sutent, Pfizer).

Seventy-five percent to 80% of patients with advanced renal cell carcinoma have intermediate- or poor-risk disease, which historically is associated with a poor prognosis. One-year OS for advanced renal cell carcinoma is 36%, with a 5-year OS of only 8%.

“Physicians treating advanced renal cell carcinoma have had few options to help achieve the goal of improved survival,” Robert J. Motzer, MD, medical oncologist and Jack and Dorothy Byrne chair in clinical oncology at Memorial Sloan Kettering Cancer Center, said in a company-issued press release. “Data from the CheckMate-214 trial demonstrated superior OS with Opdivo plus Yervoy, showing the potential for the combination to become a new standard of care for patients with intermediate- and poor-risk advanced renal cell carcinoma.”

Researchers randomly assigned patients to receive 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses followed by 3 mg/kg nivolumab monotherapy every 2 weeks (n = 425), or 50 mg sunitinib daily for 4 weeks followed by 2 weeks off every cycle (n = 422).

Results showed significantly improved median OS in the combination arm compared with the sunitinib arm (not reached vs. 25.9 months; HR = 0.63; 95% CI, 0.44-0.89). Researchers observed this OS benefit regardless of PD-L1 expression level.

Also, researchers reported a higher overall response rate in the combination arm (41.6% vs. 26.5%; P < .0001) — including a higher rate of complete (9.4% vs. 1.2%) and partial (32.2% vs. 25.4%) response — as well as a longer duration of response (not reached vs. 18.2 months)

Median PFS reached 11.6 months for the combination and 8.4 months with sunitinib, which did not represent a significant difference (HR = 0.82; 99.1% CI, 0.64-1.05).

An independent data monitoring committee recommended the trial stop early after a planned interim analysis showed the nivolumab-ipilimumab combination improved OS and ORR, the study’s two coprimary endpoints.

Researchers could not establish the efficacy of the combination among favorable-risk patients.

Fewer patients assigned the combination than sunitinib experienced grade 3 or grade 4 adverse events (65% vs. 76%). However, more patients assigned the combination discontinued treatment due to an adverse event (31% vs. 21%) and experienced dose delay (54% vs. 43%).

The most common adverse events associated with nivolumab and ipilimumab included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia and decreased appetite.

As HemOnc Today previously reported, this application received breakthrough therapy designation and priority review.

“Our goal is to provide cancer patients with medicines that have the potential to extend their lives. As the first treatment option to increase OS for subgroups of patients with advanced renal cell carcinoma compared to sunitinib, the Opdivo plus low-dose Yervoy combination helps deliver on that promise,” Johanna Mercier, head of U.S. Commercial at Bristol-Myers Squibb, said in the press release. “This approval demonstrates our commitment to bringing immuno-oncology treatments that may improve outcomes to a broader range of renal cell carcinoma patients.”

The FDA today approved the combination of nivolumab and ipilimumab for the treatment of intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma.

The FDA based this decision on data from 847 intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma from the randomized open-label CheckMate-214 trial, which compared the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) with sunitinib (Sutent, Pfizer).

Seventy-five percent to 80% of patients with advanced renal cell carcinoma have intermediate- or poor-risk disease, which historically is associated with a poor prognosis. One-year OS for advanced renal cell carcinoma is 36%, with a 5-year OS of only 8%.

“Physicians treating advanced renal cell carcinoma have had few options to help achieve the goal of improved survival,” Robert J. Motzer, MD, medical oncologist and Jack and Dorothy Byrne chair in clinical oncology at Memorial Sloan Kettering Cancer Center, said in a company-issued press release. “Data from the CheckMate-214 trial demonstrated superior OS with Opdivo plus Yervoy, showing the potential for the combination to become a new standard of care for patients with intermediate- and poor-risk advanced renal cell carcinoma.”

Researchers randomly assigned patients to receive 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses followed by 3 mg/kg nivolumab monotherapy every 2 weeks (n = 425), or 50 mg sunitinib daily for 4 weeks followed by 2 weeks off every cycle (n = 422).

Results showed significantly improved median OS in the combination arm compared with the sunitinib arm (not reached vs. 25.9 months; HR = 0.63; 95% CI, 0.44-0.89). Researchers observed this OS benefit regardless of PD-L1 expression level.

Also, researchers reported a higher overall response rate in the combination arm (41.6% vs. 26.5%; P < .0001) — including a higher rate of complete (9.4% vs. 1.2%) and partial (32.2% vs. 25.4%) response — as well as a longer duration of response (not reached vs. 18.2 months)

Median PFS reached 11.6 months for the combination and 8.4 months with sunitinib, which did not represent a significant difference (HR = 0.82; 99.1% CI, 0.64-1.05).

An independent data monitoring committee recommended the trial stop early after a planned interim analysis showed the nivolumab-ipilimumab combination improved OS and ORR, the study’s two coprimary endpoints.

Researchers could not establish the efficacy of the combination among favorable-risk patients.

Fewer patients assigned the combination than sunitinib experienced grade 3 or grade 4 adverse events (65% vs. 76%). However, more patients assigned the combination discontinued treatment due to an adverse event (31% vs. 21%) and experienced dose delay (54% vs. 43%).

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The most common adverse events associated with nivolumab and ipilimumab included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia and decreased appetite.

As HemOnc Today previously reported, this application received breakthrough therapy designation and priority review.

“Our goal is to provide cancer patients with medicines that have the potential to extend their lives. As the first treatment option to increase OS for subgroups of patients with advanced renal cell carcinoma compared to sunitinib, the Opdivo plus low-dose Yervoy combination helps deliver on that promise,” Johanna Mercier, head of U.S. Commercial at Bristol-Myers Squibb, said in the press release. “This approval demonstrates our commitment to bringing immuno-oncology treatments that may improve outcomes to a broader range of renal cell carcinoma patients.”