The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) adopted a positive opinion recommending approval of the Opdivo ( Nivolumab ) plus low-dose Yervoy ( Ipilimumab ) combination to include first-line treatment for patients with intermediate- and poor-risk advanced renal cell carcinoma ( RCC ).

The CHMP recommendation is based on positive data from the phase 3 CheckMate -214 clinical trial, which was stopped early following a planned interim analysis that showed the combination of Opdivo 3 mg/kg plus Yervoy 1 mg/kg demonstrated a significant increase in overall survival ( OS ) with a 37% decreased risk of death in intermediate- and poor-risk patients, regardless of PD-L1 expression level, compared to a current standard of care, Sunitinib ( hazard ratio [ HR ] 0.63; 99.8% Confidence Interval [ CI ]: 0.44 to 0.89; p less than 0.0001 ).
Median overall survival in patients treated with Nivolumab plus low-dose Ipilimumab was not yet reached ( 95% CI: 28.2 to not estimable [ NE ] ), compared to 25.9 months for patients treated with Sunitinib.
Nivolumab plus low-dose Ipilimumab also delivered durable responses with a higher objective response rate of 41.6% ( 95% CI: 36.9 to 46.5; p less than 0.0001; n=177/425 ) versus 26.5% for Sunitinib ( 95% CI: 22.4 to 31.0; n=112/422 ).
Median duration of response ( durability ) for Nivolumab plus low-dose Ipilimumab was not yet reached ( 95% CI: 21.8 to NE ) among responded patients, compared to 18.2 months for Sunitinib ( 95% CI: 14.8 to NE ).
The overall safety profile was consistent with prior studies of Nivolumab in combination with low-dose Ipilimumab.

In CheckMate -214 425 patients received Nivolumab 3 mg/kg plus Ipilimumab 1 mg/kg every three weeks for four doses, followed by Nivolumab 3 mg/kg every two weeks, and 422 patients received Sunitinib 50 mg once daily for four weeks, followed by two weeks off every cycle.

The co-primary efficacy outcome measures of the trial were overall survival, objective response rate ( complete response + partial response ) and progression-free survival as determined by an independent radiographic review committee ( IRRC ) in intermediate- and poor-risk patients.
Patients were included regardless of their PD-L1 status.

Renal cell carcinoma is the most common type of kidney cancer in adults, accounting for more than 140,000 deaths worldwide each year.
Clear-cell RCC is the most prevalent type of renal cell carcinoma and constitutes 80% to 90% of all patients.
Renal cell carcinoma is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe.
Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 12.1%. ( Xagena_2018 )

Source: BMS, 2018

Xagena_Medicine_2018