Abstract
BackgroundThe primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment.MethodsTreatment-naïve patients received pazopanib according to standard of care. Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0.25.ResultsThirteen patients were included. One patient experienced dose limiting toxicity (DLT) at dose level 3 (grade 4 hypoglycemia). Maximum tolerated dose was not reached with a recommended dose of 36 Gy/3 having a probability of DLT of 11%. One-year local control was 83% (95% confidence interval 61–100) and 1-year progression-free survival was 28% (95% confidence interval 1–55).ConclusionsSBRT in combination with pazopanib is well tolerated with good local control and response rates outside the radiation field.Trial registrationThis trial was retrospectively registered on clinicaltrials.gov(NCT02334709) on January 6th, 2015.
Highlights
The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment
Dendritic cells (DCs) were characterized by the CD45+ lineagephenotype, plasmacytoid DCs were CD123 + BDCA2+ BDCA3- BDCA1- and myeloid DCs were divided into CD123- BDCA2- BDCA1+ and BDCA3+ cells
Peripheral blood mononuclear cell (PBMC) were fixed and permeabilized using Live/dead® fixable aqua dead cell stain (BD Biosciences) after surface staining, and stained with mouse anti-human monoclonal antibodies against CTLA-4, progressive disease (PD)-1 PE-Texas Red, Lag3 PE-Cy7, Tim3 FITC and FoxP3 APC antibodies
Summary
The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment. Renal cell carcinoma (RCC) presents with metastatic disease in about 30% of patients, while another 30% of patients will develop metastases [1, 2]. Durable responses are rare and most patients eventually develop progressive disease [4, 5]. PD-1/PD-L1 (programmed cell death ligand) targeting agents, especially nivolumab, have shown durable responses, but only in a minority of. Our primary objective was to determine the maximum tolerated dose (MTD) of SBRT in combination with a fixed dose of pazopanib in patients with metastatic clear cell RCC (ccRCC). Secondary end points included objective response of the non-irradiated lesions, local control, and progression-free survival (PFS). An exploratory endpoint was to assess immunologic responses using peripheral blood samples
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