Key points are not available for this paper at this time.
e16506 Background: Non-clear cell RCC (nccRCC) represents a heterogeneous group of tumors with sparse data on the clinical features and genomic landscape. Here, we describe a real-world cohort of nccRCC patients, characterize the genomic makeup, and report on clinical outcomes utilizing contemporary therapeutic strategies. Methods: Patients with nccRCC treated at Indiana University and who underwent genomic sequencing between 2015-2023 were included in this analysis. Baseline demographic and disease characteristics were summarized. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) using the log rank test to compare groups. Results: 55 patients were included. The median age at diagnosis was 56 years. 48 patients (87%) had metastatic disease. 25 (45.5%) had de novo metastatic disease. The most common histology subtypes included were unclassified (n=18; 32.7%), papillary (n=14; 25.5%), chromophobe (n=6; 10.9%), translocation (n=5; 9.1%), renal medullary (n=3; 5.5%), collecting duct (n=3; 5.5%), and other (n=6; 11.0%). Rhabdoid and/or sarcomatoid features were present in 32% (n=18). First-line systemic therapy for metastatic disease was single agent tyrosine kinase inhibitor (TKI) in 14 patients (29.2%), combination immunotherapy (IO-IO) for 11 patients (23.0%), combination IO-TKI for 11 patients (23.0%), single agent IO for 2 patients (4.2%), cisplatin-gemcitabine in 5 (10%), and other in 5 patients (10%). Genomic alterations are summarized in the table. Overall, diverse mutations were detected across variant subtypes, including alterations in TP53, CDKN2A, NF2, chromatin modulation ( SETD2, BAP1, PBRM1), PI3K/AKT (PIK3CA, PTEN, mTOR), and VHL/HIF pathway. Median PFS was 0.6 (0.3-0.9) years. No statistical difference was observed in the median PFS between the histology subgroups. 2-year OS for chromophobe histology was 100%, unclassified was 62.2%, papillary was 56%, and other histologies was 40.4%. 2-year OS for all patients treated with IO-TKI was 85.7%, single agent TKI was 47.9%, IO-IO was 38.6%, and NE for single agent IO. Conclusions: In this real-world cohort of patients with nccRCC, unclassified histology had the highest frequency of the most common genomic alterations evaluated. There was a trend with improved 2-year OS for patients with chromophobe histology and patients treated with IO-TKI. Table: see text
Taza et al. (Sat,) studied this question.