Preclinical combination studies suggest synergistic radio-sensitizing effects. The combination of TKIs with high-dose radiation is a promising approach to increase response rate. Therefore, new therapeutic approaches are needed to improve the number of patients benefiting from durable disease control. More recently, PD-1/PD-L1 (programmed cell death ligand) targeting agents, especially nivolumab, have shown durable responses, but only in a minority of patients. Nevertheless, durable responses are rare and most patients eventually develop progressive disease. Tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) are currently considered the mainstay treatment for metastatic patients in first line.

Renal cell carcinoma (RCC) presents with metastatic disease in about 30% of patients, while another 30% of patients will ultimately develop metastases. This trial was retrospectively registered on ( NCT02334709) on January 6th, 2015. SBRT in combination with pazopanib is well tolerated with good local control and response rates outside the radiation field.

One-year local control was 83% (95% confidence interval 61–100) and 1-year progression-free survival was 28% (95% confidence interval 1–55). Maximum tolerated dose was not reached with a recommended dose of 36 Gy/3 having a probability of DLT of 11%. One patient experienced dose limiting toxicity (DLT) at dose level 3 (grade 4 hypoglycemia).

Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0.25. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. Treatment-naïve patients received pazopanib according to standard of care. The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment.

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