80 Real-World Outcomes and Clinicogenomic Factors Associated with Response to Tivozanib: A Multi-Center Study

Background Tivozanib is a selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) approved refractory in metastatic renal cell carcinoma (mRCC). However, there is limited data on the real-world efficacy of this agent. Furthermore, clinicogenomic factors associated with response to tivozanib are unknown. Methods We performed a multi-center retrospective study of patients with mRCC treated with tivozanib. Clinical information, disease characteristics, and clinicogenomic data were recorded using electronic medical records. Data were used to analyze objective response rates (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Comparisons between responders and non-responders were performed using Fisher’s exact test. Genomic analysis was performed on patients with available next generation sequencing data (tissue and liquid). Results Among 123 patients with mRCC treated with tivozanib, 58 had adequate follow up data and were included in this analysis. Among this cohort, 69% were male, and 19% were Hispanic. The median age at the start of tivozanib was 63 years (range 29-85). Clear cell histology was the most common (96%), with non-clear cell histology representing 4% of patients. Sarcomatoid features were present in 19% of patients. At the start of therapy, the most common metastatic sites included lungs (79%), lymph nodes (40%), liver (34%), and bone (31%). Most patients (93%) previously had a nephrectomy, with 25% receiving prior adjuvant therapy. The median number of lines of therapy in a metastatic setting prior to tivozanib was 3 (range: 1-8). Among the 53 patients with available imaging, ORR was 17% and DCR was 51%. The median OS was 15.1 months (95% CI, 12.1-NE). The median PFS was 3.7 months (95% CI, 3.0-4.9). Treatment interruption and dose reduction occurred in 16% and 28% of patients, respectively. No differences in outcomes were observed between age groups, sites of metastatic disease, and prior therapies. Frequent genomic alterations included VHL (38%), PBRM1 (24%), SETD2 (21%), and TP53 (19%). Mutations in CDKN2A, CDKN2B, and NF1 had numerically response rates although not statistically significant. Conclusions In this notably diverse cohort (19% Hispanic) of heavily pretreated patients with mRCC and frequent rates of visceral disease, tivozanib demonstrated clinical efficacy in this population. Updated adverse events revealed no new safety signals. There were no significant associations between clinicogenomic factors and outcomes, underscoring the need to identify novel biomarkers for mRCC.