(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a kidney and bladder cancers poster session. Dr. Marit Ahrens presented the results of the SUNNIFORECAST trial of ipilimumab + nivolumab versus standard of care in non-clear cell renal cell carcinoma (non-ccRCC) and the potential role of the CPS score and tumor nephrectomy.
Non-ccRCCs are a rare and heterogeneous group of >20 histologically and molecularly defined tumors. Due to the relative rarity of these tumors, compared to ccRCC, clinical trials of non-ccRCC are limited owing to difficulty with patient enrollment into clinical trials. As such, treatment options remain limited for these patients. To date, tyrosine kinase inhibitors (TKIs) +/- immune checkpoint inhibitors (ICIs) are standard of care options for these patients. Herein, Dr. Ahrens presented the results of a prospective randomized European trial that compared ipilimumab + nivolumab (IPI+NIVO) versus standard of care in therapy-naïve, advanced non-ccRCC patients.
Eligible non-ccRCC patients were randomized 1:1 to receive either:
- Nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses, followed by a flat dose of 240 mg IV every 2 weeks or 480 mg every 4 weeks
- Standard of care therapy, per the investigator’s choice
- Treatment was continued until disease progression or intolerance
Randomization was stratified by non-ccRCC subtype (papillary versus non-papillary) and by IMDC risk score. Central pathology was mandatory to confirm the correct diagnosis of the non-ccRCC subtype according to the 2022 WHO classification.
The primary study endpoint was the 12-months overall survival (OS) rate. The secondary endpoints were:
- OS at 6 and 18 months
- OS
- Progression-free survival (PFS)
- Objective response rate (ORR)
This trial included 309 patients, of whom 71% were male. Overall, 173 patients (56%) had papillary RCC, and 143 (44%) had non-papillary subtypes:
- Chromophobe: 59
- Sarcomatoid/rhabdoid: 20
- Collecting duct: 10
- TFE3-rearranged or TFEB-altered RCC: 11
- Other: 37
IMDC scores were as follows:
- Favorable: 24%
- Intermediate: 52%
- Poor: 24%
Patients in the IPI+NIVO arm had superior 12 months OS rates (78.3% versus 68.3%, p=0.026). The median OS was 33.2 versus 25.2 months, respectively. There was no difference in median PFS (5.4 versus 5.7 months, respectively). The ORRs were 33% and 19%, respectively.
The median OS and response to the study treatments differed by the CPS score. Patients with a CPS≥1 had a 12-months OS rate of 79.3% with IPI+NIVO and 58.3% with standard of care therapy, with median OS of 38.6 and 18.8 months (p=0.007), respectively.
OS outcomes also varied by prior nephrectomy status:
- Prior nephrectomy:
- IPI+NIVO: 38.9 months
- Standard of care: 34 months
- No prior nephrectomy
- IPI+NIVO: 26.3 months
- Standard of care: 16.5 months
Dr. Ahrens concluded as follows:
- The 12-months OS rate was significantly superior for non-ccRCC patients treated with ipilimumab + nivolumab versus standard of care therapy
- Patients with a CPS score ≥1 treated with ipilimumab + nivolumab had a longer median OS
Presented by: Marit Ahrens, MD, Department of Hematology and Oncology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.