CheckMate 214: Sustained OS benefit with frontline nivolumab/ipilimumab in RCC
A combination therapy of nivolumab plus ipilimumab (NIVO + IPI) continues to confer survival benefit and durable response over 30 months of follow-up compared with sunitinib in patients with advanced renal cell carcinoma (RCC), according to updated results of CheckMate 214 presented at ASCO Genitourinary Cancers Symposium (GUCS) 2019.
The NIVO + IPI combination has recently gained the US FDA approval in 2018 for first-line treatment of patients with intermediate- and poor-risk advanced RCC, based on superior overall survival (OS) over sunitinib in the primary analysis of CheckMate 214 at a minimum follow-up of 17 months.
The updates presented at GUCS 2019 were from an extended follow-up of a minimum of 30 months, which provided further evidence that the favourable OS and response with NIVO + IPI were maintained in the long term.
At a median follow-up of 32.4 months, OS remained significantly longer in the NIVO + IPI arm compared with the sunitinib arm in the intention-to-treat (ITT) population (median, not reached vs 37.9 months, hazard ratio [HR], 0.71; p=0.0003), as well as in the subgroup of patients with intermediate or poor risk (median, not reached vs 26.6 months, HR, 0.66; p<0.0001). [GUCS 2019, abstract 547]
Similar findings were seen for progression-free survival (PFS), with HRs of 0.86 (p=0.0267) in the ITT population and 0.77 (p=0.0014) in the intermediate- or poor-risk subgroup, in favour of NIVO + IPI.
The NIVO + IPI arm also continued to show improved objective response rate (ORR) over the sunitinib arm across both the ITT population (41 percent vs 34 percent; p=0.0154) and the intermediate- or poor-risk population (42 percent vs 29 percent; p=0.0001), with complete response (CR) rates of 11 percent vs 2 percent and 11 percent vs 1 percent in the respective population.
Citing the CR rates with NIVO + IPI as “impressive”, Dr Nizar Tannir from the University of Texas MD Anderson Cancer Center in Houston, Texas, US said, “This is an efficacious, tolerable regimen that produces, so far, an unprecedented CR rate that’s durable for many patients. I think we can speak of breaking the barrier of cure with this regimen.”
“Regardless of risk, … NIVO + IPI now produces a higher CR rate than with sunitinib … [even though] there is no significant difference in response rate or PFS or survival between the two arms [in the subgroup with favourable risk],” he added.
The open-label phase III CheckMate 214 randomized 1,096 patients with advanced clear cell RCC in a 1:1 ratio to receive NIVO + IPI intravenously or sunitinib orally. Primary analysis reported previously, after a minimum follow-up of 17.5 months, showed superior OS with NIVO + IPI over sunitinib (median, not reached vs 26.0 months, HR, 0.63; p<0.001). ORRs were 42 percent vs 27 percent (p<0.001), respectively, with 9 percent vs 1 percent who achieved a CR, respectively (p<0.001).
In the current analysis, there were no new safety signals that emerged with the longer follow-up. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 47 percent of patients in the NIVO + IPI arm and 64 percent of sunitinib-treated patients.
According to the investigators, the overall burden of grade 3–4 TRAEs was lower in the NIVO + IPI arm vs the sunitinib arm, with most grade 3–4 TRAEs occurring in the first 2 months in both arms, but chronic toxicity persisted in the sunitinib arm. TRAEs leading to discontinuation were reported in one additional patient treated with NIVO + IPI and three additional patients receiving sunitinib since the primary analysis.