First-line tivozanib in favorable- and very favorable–risk metastatic renal cell carcinoma: Real-world evidence from the TIVOREAL-SOGUG study.

4547 Background: The optimal first-line treatment for favorable-risk metastatic renal cell carcinoma (mRCC) remains debated in the immune checkpoint inhibitor (ICI) era. Real-world data assessing prognostic subgroups treated with VEGFR-TKI monotherapy are limited. Methods: TIVOREAL-SOGUG is a retrospective multicenter study including patients with clear-cell mRCC treated with first-line tivozanib between 2017 and 2024 across 14 Spanish centers. Favorable-risk was defined by IMDC criteria (0 risk factors). A very favorable-risk (VFAV) subgroup was identified according to Zarba et al. criteria (time from diagnosis to systemic therapy >3 years, Karnofsky performance status 90–100%, and absence of brain, liver, or bone metastases). The primary endpoint was time to treatment failure (TTF); secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), subsequent therapies, and safety. Results: Among 198 evaluable patients, 84 (42.4%) had favorable-risk disease, including 23 (27.4%) classified as VFAV. In the overall favorable-risk cohort, ORR was 48.8%, including 7.1% complete responses. Median PFS and TTF were 23.7 and 14.7 months, respectively. Median OS was not reached, with 2- and 5-year OS rates of 85.4% and 67.8%. VFAV-risk patients showed higher ORR (65.2%), prolonged PFS (32.2 months) and TTF (31.1 months), and low primary progression. Treatment discontinuation due to toxicity occurred in 9.5% of patients. Most frequent adverse events were grade 1–2 fatigue, diarrhea, mucositis, dysphonia and hypertension, with grade ≥3 events being infrequent and mainly limited to hypertension. After progression, most favorable-risk patients received ICIs, whereas VFAV-risk patients required subsequent therapy less frequently, reflecting more durable disease control. Conclusions: In routine clinical practice, first-line tivozanib provides durable disease control and long-term survival in IMDC favorable-risk mRCC, and particularly in VFAV-risk patients. ICI and cabozantinib remain effective salvage options in this setting upon disease progression. Key clinical outcomes by prognostic subgroup. Outcome Favorable-risk (n=84) Very favorable-risk (n=23) Median TTF, months (95% CI) 14.7 (9.2–20.1) 31.1 (8.0–54.1) Median PFS, months (95% CI) 23.7 (14.1–33.3) 32.2 (21.1–43.4) ORR, % (CR %) 48.8 (7.1) 65.2 (13.0) Primary progressive disease, % 14.3 4.3 2-year OS, % (95% CI) 85.4 (77.2–92.8) 95.7 (88.1–100) Discontinuation due to toxicity, % 9.5 8.7 TTF and PFS were estimated using Kaplan–Meier methodology; tumor response was assessed according to RECIST 1.1.