Targeted Literature Review of Outcomes to Initial Systemic Therapy for Advanced/Metastatic Non-Clear Cell Renal Cell Carcinoma in Observational Studies

Background: Non-clear cell renal cell carcinoma (nccRCC) is a diverse group of cancers that occurs in approximately 25% of patients with renal cell carcinoma. In the advanced/metastatic setting, survival in all nccRCC subtypes is considered poor, due to the inherent aggressiveness of these cancers, and a lack of effective systemic treatment options. Clinical trials of immune/targeted agents have predominantly focused on patients with ccRCC. There is no globally accepted standard of care for nccRCC; however, recently clinical trials have been initiated in this population. Objective: To perform a targeted literature review of published original observational studies reporting common real-world clinical outcomes (real-world overall response rate [rwORR], real-world progression free survival [rwPFS], real-world overall survival [rwOS]) in previously treatment naive patients with advanced/metastatic nccRCC. Methods: A targeted search of MEDLINE and EMBASE was conducted per PRISMA guidelines to identify observational studies in previously treatment naive patients with advanced/metastatic nccRCC. Publications with adequate information since 2010 and from select conferences since 2020 were considered. Results: 27 studies across 29 publications were identified. Sample sizes ranged from 7-1,573 across these studies with differences in nccRCC subtypes included and treatments received. Real-world ORR ranged from 0-37%, median rwPFS from 2-17 months, and median rwOS from 3-30 months, across 19, 17, and 24 studies, respectively. These outcomes also varied with receipt/type of treatment and demographic/clinical subgroups with outcomes tending to be worse in patients with papillary RCC compared to chromophobe RCC. Conclusions: Clinical outcomes varied, as patient populations, eligible histologies, treatments and methods were heterogeneous.