The combination of ipilimumab (YERVOY) and nivolumab (OPDIVO) has shown a significant improvement in overall survival for patients with non-clear cell renal cell carcinoma (nccRCC) compared to standard of care (SOC), according to results from the SUNNIFORECAST trial presented at the European Society for Medical Oncology (ESMO) 2024 Congress. This prospective, randomized phase 2 trial is the first to compare a dual checkpoint inhibitor regimen with SOC in this patient population, addressing a critical need for effective therapies in this rare and heterogeneous group of cancers.
Improved Overall Survival
The SUNNIFORECAST trial demonstrated a statistically significant improvement in the 12-month overall survival rate with the ipilimumab/nivolumab combination. The overall survival rate at 12 months was 86.9% (95% CI, 80.24 – 91.46) in the combination arm compared to 76.8% (95% CI, 68.62 – 83.09; P = .0141) in the SOC arm. Median overall survival was 42.4 months (95% CI, 35.24 – 55.54) for the ipilimumab/nivolumab arm versus 33.9 months in the SOC arm (P = .292).
Professor Lothar Bergmann, chair of the hematology/oncology section at the University Cancer Centre in Frankfurt, highlighted the clinical relevance of these findings, stating, "This randomized SUNNIFORECAST trial underlines a relevant clinical benefit of the combination in non-clear cell real cell carcinoma and may possibly be the new standard in these entities."
Trial Design and Patient Population
The trial enrolled treatment-naïve patients with nccRCC, randomizing them 1:1 to either nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses, followed by nivolumab 240 mg IV every 2 weeks or 480 mg every 4 weeks, or SOC as determined by the investigators. Patients were stratified based on papillary versus non-papillary cancers per International Metastatic RCC Database Consortium (IMDC) Risk Score. The primary endpoint was overall survival rate at 12 months, with secondary endpoints including overall survival at 6 and 18 months, progression-free survival (PFS), overall response rate (ORR), time to progression (TTP), and safety and quality of life outcomes.
The study included 157 patients in the ipilimumab/nivolumab arm and 152 in the SOC arm. The median age was 62.3 years, with 70.9% being male. A majority (52.4%) had a Karnofsky score of 100. SOC was predominately tyrosine kinase monotherapy.
Efficacy and Safety Outcomes
While the primary endpoint of overall survival was met, the combination therapy did not achieve statistically significant improvements in ORR (25.4% vs 23.3%) or median PFS (5.09 months vs 5.55 months) compared to SOC. However, each secondary endpoint was superior to the SOC arm.
Regarding safety, the combination therapy showed a manageable safety profile, with no new adverse events reported. The most frequently observed adverse events in the treatment arm included skin reactions (48.4%), fatigue (42.9%), and pruritus (25.0%).
Implications for Clinical Practice
Non-clear cell renal cell carcinomas represent a rare and heterogeneous group of cancers with limited robust clinical trial data to guide treatment decisions. The SUNNIFORECAST trial provides valuable evidence supporting the use of ipilimumab/nivolumab as a potential new standard of care for these patients. Further analysis and international collaboration are needed to continue improving outcomes for individuals with nccRCC.
