SBRT Plus Nivolumab/Ipilimumab Fails to Improve PFS in Advanced RCC

Stereotactic body radiation therapy (SBRT) plus nivolumab (Opdivo) and ipilimumab (Yervoy) failed to improve progression-free survival (PFS) vs nivolumab and ipilimumab alone in patients with advanced renal cell carcinoma (RCC), according to data from the phase 2 CYTOSHRINK trial (NCT0490710) that were presented at the 2026 Genitourinary Cancers Symposium.

Among patients treated in the intent-to-treat population, the median PFS was 10.2 months (95% CI, 5.1-18.1) in the control arm (n = 24) vs 6.3 months (95% CI, 3.9-11.7) in the SBRT arm. Moreover, the 12-month PFS rates among patients treated in each arm were 47.8% (95% CI, 26.8%-66.1%) vs 34.9% (95% CI, 21.2%-48.9%), respectively (HR, 1.20; 95% CI, 0.65-2.21; P = .56).

A per protocol (PP) analysis showed that among patients treated with 4 cycles of the immunotherapy combination alone (n = 16) or with SBRT (n = 24), the median PFS was 13.7 months (95% CI, 5.1-not reached [NR]) vs 11.5 months (95% CI, 5.8-NR), respectively. The respective 12-month PFS rates were 56.3% (95% CI, 29.5%-76.2%) vs 45.8% (95% CI, 25.6%-64.0%; HR, 1.07; 95% CI, 0.46-2.45; P = .88).

Additionally, the objective response rate (ORR) in the respective arms across the ITT population was 41.6%% vs 32.5%. Ongoing responses were observed among 10% vs 50% of responders in the control and SBRT arms. The median overall survival (OS) was not reached (NR) in either arm, and the 1-year OS rates were 86.7% (95% CI, 64.3%-95.5%) and 72.1% (95% CI, 56.1% vs 83.1%).

“CYTOSHRINK is the first randomized trial testing the addition of early cytoreductive SBRT [to] first-line [nivolumab/ipilimumab] for [patients with] de novo advanced RCC,” Aly-Khan Lalani, MD, FRCPC, chair of the Genitourinary Cancers Disease Site Team at the Juravinski Cancer Centre and associate professor of Oncology at McMaster University, stated in the presentation. “While 12-month PFS was not improved compared with [nivolumab/ipilimumab] alone, there were some notable baseline imbalances. The addition of SBRT to [nivolumab/ipilimumab] was safe, with no new safety signals related to either modality.”

The phase 2 trial was conducted across 7 sites across Canada and Australia, and investigators enrolled patients presenting with biopsy proven untreated poor- or intermediate-risk de novo metastatic RCC. Patients were randomly assigned in a 2:1 ratio to receive nivolumab/ipilimumab alone or with SBRT at 30 to 40 Gy in 5 fractions. SBRT was administered to the primary kidney mass between cycles 1 and 2 of treatment.

Among patients in the SBRT and control arms, the mean age was 62 years (SD, 9.3) vs 66 years (SD, 7.9), and 72% vs 75% were male. Additionally, most patients across both arms had intermediate IMDC risk (58% vs 58%). In the experimental and control arms, 70% vs 46% had T3/T4 stage disease, 23% vs 8% had liver metastases, and the median primary target lesion size was 97 mm vs 87.5 mm.

The primary end point of the study was PFS at 1 year. Secondary end points included safety, OS, ORR, health-related quality of life, and correlative biomarker analyses.

Regarding safety, grade 3/4 adverse effects (AEs) occurred in 54% vs 65% of the control and SBRT arms. Grade 3/4 treatment-related AEs (TRAEs) occurred in 29% vs 23%. The most common grade 3/4 TRAEs in each arm included adrenal insufficiency (n = 2,1); fatigue (n = 2,0); increases in alanine transaminase, aspartate aminotransferase, and hepatic serum blood panel (n = 2, 2); colitis (n = 1, 3); and rash (n = 1, 1).

Reference

Lalani AK, Pond GR, Siva S, et al. CYTOSHRINK: a randomized phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with ipilimumab/nivolumab for metastatic kidney cancer. J Clin Oncol. 2026;44(suppl 7):416. doi:10.1200/JCO.2026.44.7_suppl.416