Results from the phase 3 CheckMate -214 trial evaluating Nivolumab ( Opdivo ) plus Ipilimumab ( Yervoy ) versus Sunitinib ( Sutent ) in patients with previously untreated advanced or metastatic renal cell carcinoma ( RCC ), including data on key subgroups were presented at the European Society for Medical Oncology ( ESMO ) Congress.
With a minimum follow-up of 17.5 months, Nivolumab in combination with Ipilimumab reduced the risk of death 37% [ hazard ratio, HR=0.63; 99.8% CI: 0.44 to 0.89; P less than 0.0001 ] compared with Sunitinib, the current standard of care, in an interim analysis of overall survival ( OS ) in intermediate- and poor-risk patients, the co-primary endpoint.
The median overall survival had not yet been reached for the combination and was 26 months for Sunitinib ( 95% CI: 22.1 to NA ).
The Nivolumab plus Ipilimumab combination also improved overall survival in all randomized patients, a secondary endpoint. In this population, the combination reduced the risk of death 32% [ HR=0.68; 99.8% CI: 0.49 to 0.95; P=0.0003 ] compared with Sunitinib.
The median overall survival had not yet been reached for the combination and was 32.9 months for Sunitinib ( 95% CI: NA to NA ).
Results for objective response rate ( ORR ) and progression-free survival ( PFS ) in intermediate- and poor-risk patients, the two other co-primary endpoints, were previously reported.
The safety of the combination was consistent with that observed in previously reported studies of these medicines in patients with renal cell carcinoma.
Adverse events leading to discontinuation were reported in 22% of patients ( n=547 ) in the combination group, compared with 12% of patients in the Sunitinib group ( n=535 ).
The most common grade 3/4 adverse effects in the combination group were fatigue ( 4% ), diarrhea ( 4% ), rash ( 2% ), nausea ( 2% ), and, in less than 1% each, pruritus, hypothyroidism, vomiting and hypertension.
In the Sunitinib group, the most common grade 3/4 adverse effects were hypertension ( 16% ), fatigue ( 9% ), palmar-plantar erythrodysaesthesia syndrome ( 9% ), stomatitis ( 3% ), mucosal inflammation ( 3% ), vomiting ( 2% ), nausea ( 1% ), decreased appetite ( 1% ), hypothyroidism ( less than 1% ) and dysgeusia ( less than 1% ).
There were seven treatment-related deaths in the combination group and four in the Sunitinib group.
In CheckMate -214 patients in the combination group received Nivolumab 3 mg/kg plus Ipilumab 1 mg/kg every 3 weeks for 4 doses followed by Nivolumab 3 mg/kg every 2 weeks.
Patients in the comparator group received Sunitinib 50 mg once daily for 4 weeks, followed by 2 weeks off before continuation of treatment.
Patients were treated until progression or unacceptable toxic effects.
The primary endpoints of the trial are progression-free survival, overall survival and objective response rate in an intermediate to poor-risk patient population ( approximately 75% of patients ). Safety is a secondary endpoint.
In previously reported trial the combination of Nivolumab plus Ipilimumab achieved an ORR of 42% versus 27% for Sunitinib in poor- and intermediate-risk patients, a co-primary endpoint.
Median duration of response was not reached for the combination and was 18.2 months for Sunitinib.
Progression-free survival in intermediate- and poor-risk patients, a co-primary endpoint, improved 18% for those receiving the combination ( HR=0.82; 99.1% CI: 0.64 to 1.05; stratified two-sided p=0.0331 ) but did not reach the pre-defined statistical significance threshold of 0.009 compared with Sunitinib.
The median progression-free survival for the combination group was 11.6 months ( 95% CI: 8.7 to 15.5 ) versus 8.4 months ( 95% CI: 7.0 to 10.8 ) for the Sunitinib group.
Renal cell carcinoma is the most common type of kidney cancer in adults, accounting for more than 100,000 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 )
Source: BMS, 2017