SBRT Addition Shows No PFS Benefit in Advanced Renal Cell Carcinoma

The addition of stereotactic body radiation therapy (SBRT) to the immunotherapy combination of ipilimumab (Yervoy) and nivolumab (Opdivo) did not improve progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), according to results from the phase 2 CYTOSHRINK trial presented at the 2026 ASCO Genitourinary Cancers Symposium.

CYTOSHRINK Trial Findings

The CYTOSHRINK trial (NCT0490710) investigated the potential benefit of adding early cytoreductive SBRT to first-line nivolumab/ipilimumab for patients with de novo advanced RCC. The study was conducted across seven sites in Canada and Australia.

Progression-Free Survival

In the intent-to-treat (ITT) population, the median PFS was 10.2 months (95% CI, 5.1-18.1) in the control arm (nivolumab/ipilimumab alone, n = 24) compared to 6.3 months (95% CI, 3.9-11.7) in the SBRT arm. The 12-month PFS rates were 47.8% (95% CI, 26.8%-66.1%) versus 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, focusing on patients who received 4 cycles of immunotherapy alone (n = 16) or with SBRT (n = 24), showed a median PFS of 13.7 months (95% CI, 5.1-not reached [NR]) versus 11.5 months (95% CI, 5.8-NR), respectively. The 12-month PFS rates were 56.3% (95% CI, 29.5%-76.2%) and 45.8% (95% CI, 25.6%-64.0%; HR, 1.07; 95% CI, 0.46-2.45; P = .88).

Objective Response Rate and Overall Survival

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

Safety Profile

SBRT was considered safe when added to the immunotherapy combination. Grade 3/4 adverse events (AEs) occurred in 54% of patients in the control arm and 65% in the SBRT arm. Grade 3/4 treatment-related AEs (TRAEs) occurred in 29% versus 23%, respectively. Common grade 3/4 TRAEs included adrenal insufficiency, fatigue, and increases in liver enzymes.

Study Details

Patients with biopsy-proven, untreated, poor- or intermediate-risk de novo metastatic RCC were randomized 2:1 to receive nivolumab/ipilimumab alone or with SBRT (30 to 40 Gy in 5 fractions) administered to the primary kidney mass between cycles 1 and 2 of treatment.

The mean age of patients was 62 years (SD, 9.3) in the SBRT arm and 66 years (SD, 7.9) in the control arm. Most patients in both arms had intermediate IMDC risk (58% vs 58%).

Conclusion

While the addition of SBRT to first-line nivolumab/ipilimumab did not significantly improve PFS in patients with advanced RCC, the combination was found to be safe. Further research is needed to identify biomarkers that may predict which patients could benefit from the addition of SBRT to immunotherapy.