Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology—Renal Tumor Study Group (SIOP‐RTSG)‐related retrospective descriptive study

Introduction Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology–Renal Tumor Study Group (SIOP‐RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. Methods This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti‐programmed cell death 1 (PD‐(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced‐stage and relapsed pediatric RCC. Results Of the 31 identified patients (0–18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT‐RCC) (21/31) and the remaining patients mainly presented with papillary or clear‐cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono‐ or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. Conclusion This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies. This is the first SIOP‐RTSG retrospective study that reports response‐ and survival data of pediatric patients with renal cell carcinoma (RCC) who were treated with targeted therapy. Thirty‐one patients with advanced‐stage RCC were treated with 17 different treatment regimens, highlighting current treatment heterogeneity. This descriptive study emphasizes the need for continued registration of pediatric RCC and uniform treatment with sunitinib until other targeted therapies have been further investigated, for instance using RCC organoids.