SUNNIFORECAST: Improved OS With Ipilimumab/Nivolumab in Non-Clear Cell RCC

The SUNNIFORECAST trial (LBA75), presented by Dr. Lothar Bergmann from Germany on Friday, September 13, at the European Society for Medical Oncology Congress 2024, is a prospective randomized phase 2 trial of ipilimumab/nivolumab versus the standard of care in non-clear cell renal cell cancer (nccRCC).

Patients with metastatic nccRCC were randomized (1:1) to nivolumab 3mg/kg IV plus ipilimumab 1mg/kg for 4 cycles (ipi/nivo) followed by maintenance nivolumab or standard of care (SOC) physician’s choice. Patients were stratified by histology, either papillary or non-papillary, and by IMDC score.

There were 299 patients enrolled, with a median age of 62.3 years. The majority of patients were male (70.9%). According to the IMDC score, 23.9% were low, 51.8% intermediate, and 24.3% high-risk. Most patients (68.9%) had prior nephrectomy/partial nephrectomy. Histology breakdown for patients enrolled was 57.6% papillary, 19.4% chromophobe, 5.5% translocation type, and 1.0% medullary.

This study met its overall survival (OS) endpoint at 12 months in favor of the combination immunotherapy arm: 86.9% 12-month OS for ipi/nivo versus 76.8% for SOC (P=.0141), with a difference of 42.4 months versus 33.9 months. The majority of patients in the SOC arm received TKI monotherapy.

Regarding the subgroup analysis, patients with poor-risk disease, who were younger, had PD-L1 expression, or had non-papillary histologies seemed to have a greater benefit. Progression-free survival (PFS) was not significantly different (5.52 months for ipi/nivo vs 5.65 months for SOC).

In terms of overall response rate (ORR), for all patients, the results were 32.8% for ipi/nivo versus 19.6% for SOC (P=.001). By histology subtype, the response rates were papillary 29.2% versus 21.0%, non-papillary 37.7% versus 18.2%, and chromophobe 25.9% versus 11%.

No new adverse events were identified. The most common adverse events for ipi/nivo were fatigue, pruritus, diarrhea, nausea, ALT elevation, and hypothyroidism.

The invited discussant following the session, Dr. Manuela Schmidinger, noted that this trial suffers from “double heterogeneity” due to a mix of variant histologies and treatments in the comparator arm. She also said that the improved OS rate is not maintained at longer follow-up as seen for ipi/nivo in clear cell RCC.

In summary, the combination of ipi/nivo improved the 12-month OS rate compared to SOC in patients with metastatic nccRCC. Although this is a heterogeneous group of patients, Dr. Bergmann concluded that the combination of ipi/nivo may be a new standard in some of these subgroups of patients with metastatic nccRCC. Further data and translational research are needed in these very rare entities, and international cooperations are essential to obtain sufficient patient numbers.