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Clinical Trial
. 2025 Feb 6;30(2):oyae369.
doi: 10.1093/oncolo/oyae369.

Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study

Miguel Zugman  1 , David F McDermott  2 , Bernard J Escudier  3 , Thomas E Hutson  4 , Camillo Porta  5 , Elena Verzoni  6 , Michael B Atkins  7 , Brian Rini  8 , Sumanta K Pal  1
Affiliations
Clinical Trial

Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study

Miguel Zugman et al. Oncologist. .

Abstract

Background: The phase III TIVO-3 study demonstrated improvement in progression-free survival (PFS) with tivozanib compared with sorafenib in patients with 2-3 prior systemic regimens for metastatic renal cell carcinoma (mRCC).

Methods: The TIVO-3 trial enrolled patients with measurable mRCC who had received 2 or more prior systemic therapies, including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Patients were stratified by International Metastatic RCC Database Consortium risk score and type of prior treatment and were randomized 1:1 to receive tivozanib or sorafenib. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 criteria, with PFS as the primary endpoint. Safety was evaluated using Common Terminology Criteria for Adverse Events version v4.03, and statistical analyses included Cox regression for overall survival (OS) and descriptive statistics for duration of response (DOR). The current post-hoc long-term follow-up analysis consists of an assessment of OS in the previously stratified subpopulation of patients with prior CPI exposure.

Results: Between May 2016, and August 2017, 350 patients were randomized, of which 26% had prior CPI exposure, with final analysis data cut off on June 21, 2021. In patients previously treated with CPIs (n = 91), the median PFS of tivozanib was 7.3 months versus 5.1 months with sorafenib and hazard ratio (HR) of 0.55 (95% CI, 0.32-0.94). The OS HR in the CPI-treated subset was 0.69 (95% CI, 0.43-1.11, P =.0992) favoring tivozanib, although with a median OS of 18.1 and 20.9 months, for tivozanib and sorafenib, respectively. Tivozanib demonstrated a longer median DOR of 20.3 versus 5.7 months for sorafenib in the subset previously treated with CPIs. The safety profile favored tivozanib, with lower rates of VEGF-TKI class-related grade ≥3 adverse events compared with sorafenib. However, in the subset of patients previously treated with CPIs, the incidence of grade ≥3 adverse events was higher, at 58% for tivozanib and 67% for sorafenib, compared with the ITT population, at 46% and 55%, respectively.

Conclusions: In this long-term post-hoc update of the TIVO-3 trial, we show that in CPI-resistant mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with improved OS data, although not statistically significant, and durable responses.

Keywords: immunotherapy; metastatic renal cell carcinoma; sorafenib; tivozanib; vascular endothelial growth factor inhibitor.

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Conflict of interest statement

Miguel Zugman has no conflicts of interest that might be relevant to the contents of this manuscript.

Sumanta K. Pal, MD: Consulting: Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen, Bristol Myers Squibb, Astellas Pharma, GlaxoSmithKline; Honoraria: Novartis, Medivaton, Astellas Pharma; Funding: Eisai, Pfizer, Bristol Myers Squibb, Aveo, Nektar Therapeutics, Exelixis, and QED.

David F. McDermott, MD: reported honoraria from BMS, Pfizer, Merck, Alkernes, EMD Serono, Eli Lilly and Company, Iovance, Eisai, Werewolf Therapeutics, Calithera Biosciences, and research funding from BMS, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, and Alkermes.

Bernard J. Escudier, MD: reported consulting/advisory relationships with Pfizer, BMS, Ipsen, Aveo, and Eisai.

Thomas E. Hutson, DO, PharmD: reported consulting/advisory relationships with Aveo, Pfizer, Exelixis, BMS, EMD Serono, Eisai, Jansen, Gilead, and Astellas.

Camillo Porta, MD: Consulting and/or speaking: Angelini Pharma, AstraZeneca, BMS, Eisai, Exelixis, Genenta, Ipsen, Merck Serono, MSD; protocol steering committee member: Eisai, MSD; Data Monitoring Commitee member: Genenta.

Elena Verzoni, MD: reported consulting/advisory relationships with Bristol Myers Squibb, Eisai, Janssen, Merck, MSD, and Ipsen.

Michael B. Atkins, MD: Advisory Board/Consultant: AbbVie, Agenus, Asher Bio, AstraZeneca, Atreca, Aveo, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Exelixis, GSK, Merck, Novartis, OncoRena, Pfizer, Pliant Therapeutics, Pyxis Oncology, Roche, SAB Bio, Sanofi, ScholarRock, SeaGen, Simcha, Syncona, Takeda, and Werewolf Pharmaceuticals; Stock/Stock Options: Werewolf, Pyxis Oncology.

Brian Rini, MD: Advisory Board: AVEO, BMS, Debiopharm, Eisai, EUSA, Genentech/Roche, Merck, Pfizer, Merck. Partnership on podcasts and meeting: MashupMD. Coordinating PI: Adela, Daiichi Sankyo, Surface Oncology. Local PI: Astra-Zeneca. Funding: AVeo, BMS, Janssen. Steering Committee Member: Pfizer.

Figures

Figure 1.
Figure 1.
Overall survival in patients receiving prior CPI.
See this image and copyright information in PMC

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