Tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CI) have been established as effective treatment for mRCC, but only a minority of patients achieves complete response and additional strategies are necessary to improve the efficacy of these agents. We have designed a prospective phase 1b “Volga” study to determine the safety and efficacy of extracranial SBRT in patients with clear-cell mRCC.
Patients were included if they had stable disease for at least 4 months on TKI or CI. SBRT was delivered to an organ with multiple comparable lesions, where one lesion was in the treatment target (target lesion) and the other one was intentionally left untreated (control lesion). Dose of radiation and number of fractions were determined based on target lesion localization and the proximity of organs at risk. Response in both target and control lesions was scored using RECIST 1.1 criteria at least 2 months after completion of SBRT.
17 patients were enrolled, 12 of them received TKI and 5 patients received nivolumab. SBRT was delivered to lungs (n = 5), bones (n = 4), lymph nodes (n = 4), liver (n = 1), primary RCC (n = 1), and locally recurrent RCC (n = 2). Equivalent Dose (EQD) with alpha/beta ratio of 2.6 was 114 Gy (range, 40-276 Gy). With a median follow-up of 8 months (range, 3-18), cumulative rate of SBRT-related toxicity (grade 1) was 12% (n = 2), consisting of esophagitis (n = 1) and skin erythema (n = 1). No grade 2 or higher toxicity was detected. Radiographic response in the target lesion was seen in 13 patients (76%), with complete response in 5 (29%) patients and partial response in 8 (47%) including abscopal effect in 1 patient. Control lesions were stable in 16 patients. The difference between response in target and control lesions as judged by mean sizes of these lesions before and at 2 months after SBRT was statistically significant (P < 0.01). Fraction size of equal to or greater than 10 Gy was associated with complete response in the target lesion.
Extracranial SBRT in patients with mRCC treated with TKI or CI is well tolerated and could be effective. This approach will be studied in an expanded cohort of patients.
Clinical trial identification
Legal entity responsible for the study
Kidney Cancer Research Bureau.
Has not received any funding.
All authors have declared no conflicts of interest.