OS benefit of first-line NIVO + IPI holds out through 5 years over sunitinib in sarcomatoid RCC

First-line treatment with a combination of nivolumab plus ipilimumab (NIVO + IPI) continues to show long-term survival benefits over sunitinib out to 5 years in patients with advanced clear-cell renal carcinoma (RCC) with sarcomatoid features, according to the CheckMate 214 study presented at GUCS 2022.

Over a minimum follow-up of 5 years, NIVO + IPI led to significantly longer overall survival (OS; median, 49 vs 14 months; hazard ratio [HR], 0.46; p=0.0004) as well as progression-free survival (PFS; median, 26 vs 5 months; HR, 0.50; p=0.0036) over sunitinib — benefits which were sustained over the years. [GUCS 2022, abstract 352]

Objective response rate (ORR) was also significantly higher in the NIVO + IPI group vs the sunitinib group (61 percent vs 23 percent), with complete response rates of 23 percent vs 6 percent, respectively.

The current post hoc analysis included 139 patients with intermediate/poor-risk sarcomatoid RCC (sRCC), which represented a subset of the original CheckMate 214 cohort, who had been followed up for a minimum of 5 years.

“sRCC is an aggressive histologic growth pattern in RCC with a poor prognosis and limited therapeutic options,” explained presenting author Dr Nizar Tannir of The University of Texas MD Anderson Cancer Center, Texas, Houston US. “About 5 percent of patients with RCC have sarcomatoid features, including up to 20 percent of patients with advanced disease.”

“Among the many patient populations who are likely to benefit from receiving ipilimumab in combination with nivolumab as first-line therapy, patients with advanced RCC and the presence of sarcomatoid features in the primary renal tumour or a metastatic site should be at the top of the list for the use of ipilimumab when prescribing immuno-oncology–based regimens,” he stressed.

Expression of PD-L1 in sRCC tumours may be higher than clear-cell RCC without the presence of sarcomatoid features, according to Tannir.

While survival was generally longer in the subgroup with higher tumour PD-L1 expression than those with <1 percent PD-L1 levels, the OS benefit of NIVO + IPI remained regardless of whether PD-L1 levels were ≥1 percent (median, not reached [NR] vs 20.9 months; HR, 0.40; p=0.0143) or <1 percent (median, 40.4 vs 13.8 months; HR, 0.42; p=0.0049), compared with sunitinib.

Similar findings were seen for PFS, in favour of NIVO + IPI (median, NR vs 5.6 months; HR, 0.29; p=0.0002 for PD-L1 ≥1 percent; and median, 9.0 vs 5.4 months; HR, 0.65; p=0.1894 for PD-L1 <1 percent).

“These findings, coupled with the durable responses observed with NIVO + IPI over sunitinib, provide compelling support for the use of NIVO + IPI as the preferred first-line therapy in all patients with intermediate/poor-risk sRCC,” said Tannir. “I, therefore, consider these results practice-changing when it comes to the treatment of this subgroup of patients with advanced sRCC.”

“Additionally, the durability of responses with NIVO + IPI beyond 5 years underscores the critical role of CTLA-4 blockade when combined with PD-1 blockade to achieve the potential of cure, especially in very aggressive tumours such as sarcomatoid clear-cell RCC,” he stated.