Nivolumab Plus Ipilimumab Prolongs Survival in Treatment-Naïve Advanced Sarcomatoid RCC

Results from a post hoc exploratory analysis of the phase 3 CheckMate 214 trial (NCT02231749) show that nivolumab (Opdivo) and ipilimumab (Yervoy) achieved significant improvements in survival vs sunitinib (Sutent) in patients with intermediate- and poor-risk renal cell carcinoma (RCC) with sarcomatoid features.¹

At 5 years of minimum follow-up, the median overall survival (OS)n was 48.6 months (95% CI, 25.2-not evaluable [NE]) with the combination (n = 74) vs 14.2 months (95% CI, 9.3-22.9) with sunitinib (n = 65; HR, 0.46; 95% CI, 0.29-0.71; P = .0004). The median progression-free survival (PFS) was 26.5 months (95% CI, 7.2-NE) and 5.5 months (95% CI, 4.1-6.9), respectively (HR, 0.50; 95% CI, 0.32-0.80; P = .0036).

“These results extend those previously reported and add further support to the preferred use of nivolumab and ipilimumab as first-line therapy in patients with intermediate- and poor-risk sarcomatoid RCC, a population with a historically high unmet medical need for safe and effective treatment options,” Nizar M. Tannir, MD, lead study author and professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, said.

In the trial, patients with previously untreated clear cell advanced RCC were randomly assigned to 3 mg/kg of intravenous nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 3 mg/kg of nivolumab, or 50 mg of oral sunitinib once daily every 4 weeks of the 6-week cycle. In this exploratory analysis, patients with advanced RCC with sarcomatoid features were identified through an independent central pathology review of archival tumor tissue or histological classification per local pathology.

Individual tumor samples were collected from nephrectomy and metastatic biopsy in CheckMate 214, and tumors with any percent sarcomatoid component were deemed sarcomatoid positive.

Additional results indicated that the combination led to improved survival regardless of tumor PD-L1 expression level. In patients with PD-L1–positive tumors (≥1%), the median OS was not reached (NR) with the combination (n = 36; 95% CI, 29.9-NE) vs 20.9 months (n = 33; 95% CI, 9.3-41.2) with sunitinib (HR, 0.40; 95% CI, 0.19-0.84; P = .0143). The median PFS was NR (95% CI, 9.1-NE) vs 5.6 months (95% CI, 2.8-6.9), respectively (HR, 0.29; 95% CI, 0.14-0.57; P = .0002).

Patients with PD-L1–negative tumors (<1%) experienced a median OS of 40.4 months (n = 35; 95% CI, 18.5-NE) with the combination vs 13.8 months (n = 29; 95% CI, 5.5-20.3) with sunitinib (HR, 0.42; 95% CI, 0.22-0.78; P = .0049). The median PFS was 9.0 months (95% CI, 3.3-47.0) vs 5.4 months (95% CI, 4.0-17.0), respectively (HR, 0.65; 95% CI, 0.34-1.24; P = .1894).

The objective response rate (ORR) was significantly higher with the combination, 60.8% (95% CI, 48.8%-72.0%) vs 23.1% (95% CI, 13.5%-35.2%) with sunitinib (P < .0001). The complete response (CR) rates were 23.0% and 6.2%, respectively.

Notably, the ORR and CR rates improved with the combination compared with sunitinib regardless of baseline tumor PD-L1 expression. Moreover, the median duration of response was not reached ([NR] 95% CI, 22.5-NE) with the combination vs 25.1 months (95% CI, 7.2-60.4) with sunitinib.

The median treatment-free interval was 2.9 months (range, 0.0-68.2) with the combination vs 1.4 months (range, 0.1-65.8) with sunitinib. In patients who discontinued therapy because of treatment-related adverse events (TRAEs), the median treatment-free interval was 12.3 months (range, 1.0-66.0) and 3.1 months (range, 0.7-65.8), respectively.

Among responders who discontinued treatment and never received subsequent therapy, 49% (n = 22/45) in the combination arm and 40% (n = 6/15) in the sunitinib arm experienced a treatment-free interval. Among responders who discontinued treatment and did receive subsequent therapy, 82% (n = 37/45) and 100% (n = 15/15) of patients experienced a treatment-free interval, respectively.

Regarding toxicity, investigators identified no new signals with either regimen in the sarcomatoid population. The safety profiles were comparable with the overall trial population.

Any-grade TRAEs occurred in 97.3% of patients who received the combination vs 96.9% of patients who received sunitinib; grade 3 or 4 TRAEs were reported in 49.3% and 44.6% of patients, respectively. TRAEs leading to discontinuation occurred more often in the combination arm (any grade, 21.9%; grade 3/4, 19.2%) vs the sunitinib arm (any grade, 12.3%; grade 3/4, 9.2%).

One treatment-related death, previously reported, occurred in a patient who received the combination. There were no deaths with sunitinib.

_REFERENCE:

_{Tannir NM, Signoretti S, Choueiri TK, et al. Efficacy and safety of nivolumab plus ipilimumab versus sunitinib for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5-year minimum follow-up. Presented at: International Kidney Cancer Symposium; November 4-5, 2022. Austin, Texas. Abstract 32.}