Nivolumab/Ipilimumab Improves Outcomes Vs Sunitinib in Sarcomatoid RCC

Nivolumab (Opdivo) and ipilimumab (Yervoy) improved responses and long-term survival compared with sunitinib (Sutent) for patients with sarcomatoid renal cell carcinoma (RCC), supporting the combination’s use as standard-of-care therapy according to findings from an exploratory analysis in the phase 3 CheckMate 214 trial (NCT02231749).

Nivolumab plus ipilimumab yielded a median overall survival (OS) of 48.6 months (95% CI, 25.2-not estimable [NE]) vs 14.2 months (95% CI, 9.3-22.9) with sunitinib (HR, 0.46; 95% CI, 0.29-0.71; P = .0004). Median progression-free survival (PFS) among patients receiving nivolumab plus ipilimumab vs those receiving sunitinib, respectively, was 26.5 months (95% CI, 7.2-NE) vs 5.5 months (95% CI, 4.1-6.9; HR, 0.50; 95% CI, 0.32-0.80; P = .0036).

The overall response rates (ORRs) in the nivolumab plus ipilimumab cohort and sunitinib cohort, respectively, were 60.8% (95% CI, 48.8%-72.0%) vs 23.1% (95% CI, 13.5%-35.2%; P <.0001). The rate of ongoing responses was 66.7% vs 40.0% and the rate of complete response was 23.0% vs 6.2% in each respective cohort. Additionally, the median duration of response was not reached (95% CI, 22.5-NE) in the combination arm vs 25.1 months (95% CI, 7.2-60.4) in the monotherapy arm.

Investigators of the global, multicenter, open-label, randomized phase 3 CheckMate 214 trial assessed nivolumab and ipilimumab combination therapy compared with sunitinib among adult patients with treatment-naïve advanced RCC. Patients were randomly assigned 1:1 to either receive 3 mg/kg of nivolumab intravenously with 1 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 3 mg/kg of nivolumab every 2 weeks, or 50 mg of oral sunitinib once a day using a 4 weeks on, 2 weeks off schedule in 6-week cycles.

The post hoc, exploratory analysis included patients with International Metastatic RCC Database Consortium intermediate- or poor-risk disease, and outcomes of interest included OS, PFS, and ORR by independent radiology review committee per RECIST v1.1 criteria. Investigators also assessed outcomes in a subgroup of patients based on baseline tumor PD-L1 expression levels.

Of 1096 patients included in the total population of the CheckMate 214 trial, 847 had intermediate- or poor-risk disease, including 425 patients receiving nivolumab plus ipilimumab and 422 receiving sunitinib. Additionally, 139 patients (16.4%) had sarcomatoid histology, including 74 in the nivolumab plus ipilimumab arm and 65 in the sunitinib arm.

Of note, 50.7% of patients receiving nivolumab plus ipilimumab with intermediate- or poor-risk sarcomatoid histology had a baseline tumor PD-L1 expression of at least 1% compared with 26.0% of all patients with intermediate- or poor-risk disease.

Additionally, in the nivolumab combination therapy and sunitinib arms, respectively, most patients with sarcomatoid histology had lung metastases at baseline (78% and 77%) along with the overall population (69% and 70%). Fourteen percent and 12% of patients with sarcomatoid histology had liver metastases in each respective treatment arm along with 21% and 21% of patients in the general population.

In all patients with sarcomatoid RCC and an evaluable baseline tumor PD-L1 expression of at least 1%, the median OS was not reached (95% CI, 29.9-NE) with nivolumab plus ipilimumab compared with 20.9 months (95% CI, 9.3-41.2) in the sunitinib arm (HR, 0.40; 95% CI, 0.19-0.84; P =.0143). Additionally, the median OS for patients with a baseline tumor PD-L1 expression less than 1% was 40.4 months (95% CI, 18.5-NE) vs 13.8 months (95% CI, 5.5-20.3) in each respective arm (HR, 0.42; 95% CI, 0.22-0.78; P = .0049).

The median PFS for patients with baseline tumor PD-L1 expression of at least 1% was not reached (95% CI, 9.1-NE) with nivolumab combination therapy vs 5.6 months (95% CI, 2.8-6.9) with sunitinib. The median PFS for those with a baseline tumor PD-L1 expression of less than 1% was 9.0 months (95% CI, 3.3-47.0) vs 5.4 months (95% CI, 4.0-17.0) in each respective arm.

The median ORR for patients with a baseline tumor PD-L1 expression at least 1% was 69.4% for those receiving nivolumab combination therapy and 24.2% for those receiving sunitinib. The median ORR among patients with a baseline tumor PD-L1 expression of less than 1% was 54.3% vs 20.7% in each respective arm.

Of those with intermediate- or poor-risk sarcomatoid RCC, grade 3/4 treatment-related adverse effects (TRAEs) occurred in 49.3% (n = 36/73) of patients receiving nivolumab combination therapy and 44.6% (n = 29/65) of those receiving sunitinib. TRAEs leading to discontinuation occurred in 21.9% (n = 16/73) and 12.3% (n = 8/65) of patients in each respective cohort.

Investigators reported 1 treatment-related death in a patient with intermediate- or poor-risk disease who received nivolumab plus ipilimumab.

Reference

Rini BI, Signoretti S, Choueiri TK, et al. Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma. J Immunother Cancer. 2022;10(12):e005445. doi:10.1136/jitc-2022-005445