Real-world efficacy and safety of tivozanib in metastatic renal cell carcinoma in a diverse cohort: A multicenter study from the City of Hope enterprise.

477 Background: Tivozanib is a selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) approved refractory metastatic renal cell carcinoma (mRCC) after 2 prior therapies. However, the safety and efficacy of tivozanib in real-world settings of patients with mRCC in non-clinical trial settings are limited. Methods: We conducted a multi-center, retrospective study of tivozanib-treated patients with mRCC from the City of Hope Cancer Center nationwide. Clinical information and disease characteristics 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). Adverse events (AEs) were also recorded and graded per CTCAE v5.0. Results: Among 123 patients with mRCC treated with tivozanib, 83 had adequate follow up data and were included in this analysis. Among this cohort, 72% were male, and 18% were Hispanic. The median age at the start of tivozanib was 66 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 16% of patients. At the start of therapy, the most common metastatic sites included lungs (81%), lymph nodes (46%), liver (37%), and bone (37%). 93% of patients previously had a nephrectomy, of whom 25% had prior adjuvant therapy. The median number of lines of therapy in a metastatic setting prior to tivozanib was 3 (range: 0-8). Among the 75 patients with available imaging, the ORR was 15% (11/75) with 1 complete response observed. The DCR rate was 48%. The median OS was 15.1 months (95% CI, 11.9-NE). The median PFS was 3.6 months (95% CI, 3.0-4.9). 87% of patients experienced any all-grade AE. The most common all-grade AEs were hypertension (36%), anemia (35%), hypothyroidism (31%), diarrhea (22%), and fatigue (19%). Common grade 3-5 AEs included fatigue (33%), diarrhea (8%), and hand-foot syndrome (8%). Treatment interruption and dose reduction occurred in 18% and 28% of patients, respectively. Six patients (7%) discontinued therapy due to an AE, among which fatigue (2%) was the most common AE leading to discontinuation. Conclusions: In this notably diverse cohort (18% Hispanic) of heavily pretreated patients with mRCC and frequent rates of visceral disease, tivozanib demonstrated clinical efficacy in this population. The toxicity profile remained largely consistent with prior experiences.