FDA Approves IO Combo for Advanced Renal Cell Cancer

Nick Mulcahy

April 16, 2018

The US Food and Drug Administration (FDA) has approved the immuno-oncology (IO) combination of nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb) as an initial treatment for advanced renal cell carcinoma (RCC) that is of intermediate or poor risk.

The approvals for each drug were based on findings from CheckMate 214, a randomized open-label trial.

The trial randomly assigned 1082 patients with previously untreated advanced RCC to receive nivolumab plus ipilimumab followed by nivolumab maintenance therapy or sunitinib (Sutent, Pfizer). Sunitinib is considered standard of care.

Efficacy was evaluated in a subpopulation of intermediate- or poor-risk patients (n = 847). The trial demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination (n = 425) compared with those receiving sunitinib (n = 422).

The median OS was not yet reached in the combination arm; it was 25.9 months in the sunitinib arm (hazard ratio, 0.63; P < .0001).

The ORR was 41.6% for the combination, vs 26.5% for the sunitinib arm (P < .0001).

The efficacy of the combination in patients with favorable-risk disease was not established and thus the combination is not approved in those patients.

"Our goal is to provide cancer patients with medicines that have the potential to extend their lives. As the first treatment option to increase overall survival for subgroups of patients with advanced RCC compared to sunitinib, the Opdivo plus low-dose Yervoy combination helps deliver on that promise," said Johanna Mercier, head, US Commercial, Bristol-Myers Squibb, in a press statement.

New Standard of Care?

Experts warmly welcomed the CheckMate 214 results when they were first presented at the European Society of Medical Oncology 2017 Congress.

For example, Maria de Santi, MD, the University of Warwick, United Kingdom, said: "This means that immunotherapy is not only a new option for these patients, it should become the standard of care."

The most common adverse reactions (in ≥20% of patients treated with the combination) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.

In the pivotal trial, the combination was associated with fewer overall grade 3 or 4 adverse events than sunitinib (65% vs 76%). However, treatment discontinuation due to adverse events occurred in 31% of patients in the combination IO arm, compared to 21% in the sunitinib arm.

The recommended schedule and dose for this combination are nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for four doses, then nivolumab, 240 mg, every 2 weeks or 480 mg every 4 weeks.

The FDA granted the applications for each of the drugs in the combination a priority review and breakthrough therapy designation.

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