1703P - Updated overall survival in patients with prior checkpoint inhibitor (CPI) therapy in the phase III TIVO-3 study

Background

The phase III TIVO-3 study demonstrated improvement in progression-free survival (PFS) with tivozanib compared to sorafenib in patients with 2-3 prior systemic therapies for metastatic renal cell carcinoma (mRCC). In the present analysis, we updated outcomes of patients with prior CPI exposure in the TIVO-3 study.

Methods

The TIVO-3 trial enrolled patients with measurable mRCC who had received 2-3 prior systemic therapies, including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk score and type of prior treatment and were randomized 1:1 to receive tivozanib or sorafenib. Efficacy was assessed using RECIST 1.1 criteria, with PFS as the primary endpoint. Safety was evaluated using CTCAE v4.03, and statistical analyses included Cox regression for overall survival (OS) and descriptive statistics for duration of response (DOR). Central to the current post-hoc analysis was 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, the median PFS of tivozanib was 7.3 months versus 5.1 months with sorafenib, hazard ratio (HR) of 0·55 (95% CI 0·32–0·94). The OS HR in the CPI-treated subset was 0.67 (95%CI: 0.42-1.08). Tivozanib also demonstrated a longer median DOR of 20.3 months versus 5.7 months 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 to 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 to 41% and 51%, respectively, in those without prior CPI therapy.

Conclusions

In this updated analysis of the TIVO-3 trial, we show that in CPI-refractory mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with a trend towards improved OS and durable responses. These data underscore tivozanib's value as a treatment option in CPI-refractory mRCC.

Clinical trial identification

NCT02627963.

Editorial acknowledgement

Legal entity responsible for the study

AVEO Oncology.

Funding

AVEO Oncology.

Disclosure

D.F. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Alkermes, Iovance, werewolf therapeutics, Calithera, Eisai; Financial Interests, Personal, Advisory Board, Scientific Advisory Board Members: Cullinan; Financial Interests, Institutional, Coordinating PI: BMS. C.G. Porta: Financial Interests, Personal, Invited Speaker, Seminars to Medical Direction Personnel on kidney cancer: Angelini; Financial Interests, Personal, Advisory Board, Consultancy relative to urogenital cancers: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisor relative to development of therapeutics in GU Oncology; speaker at BMS-sponsored meetings; protocol steering committee member: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisor role relative to the development of Lenvatinib in RCC and HCC; protocol steering committee member: Eisai; Financial Interests, Personal, Invited Speaker, Speaker at Ipsen-sponsored meeting; advisor relative to the development of Cabozantinib in RCC: Ipsen; Financial Interests, Institutional, Advisory Board, Advisor relative to the development of Pembrolizumab and Belzutifan in RCC; Speaker at MSD-sponsored meetings: MSD; Financial Interests, Personal, Advisory Board, Participation into an Advisory Board on the present scenario of urothelial cancers treatment: Merck; Financial Interests, Personal, Advisory Board, Participation into an Advisory Board on the development of novel agents for the treatment of metastatic renal cell carcinoma: Exelixis; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CLEAR study: Eisai; Financial Interests, Institutional, Steering Committee Member, Steering Committee Member of Belzutifan studies: MSD; Non-Financial Interests, Advisory Role, Unpaid consultant: Medendi, Biorek, AtG; Non-Financial Interests, Advisory Board, Member of the kidney cancer guidelines committee: Italian Association of Medical Oncology (AIOM). E. Verzoni: Financial Interests, Personal, Advisory Board: MSD, Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, Astellas, Ipsen, Pfizer; Non-Financial Interests, Principal Investigator: MSD, Ipsen, Astellas, Janssen, Lilly, Pfizer. B.I. Rini: Financial Interests, Personal, Advisory Board: Merck, BMS, Aveo, Pfizer, Eisai, Eusa, Debiopharm, Genentech/Roche; Financial Interests, Personal, Other, Partnership on podcasts and meeting: MashupMD; Financial Interests, Institutional, Coordinating PI: Merck, Surface Oncology, Daiichi Sankyo, Adela; Financial Interests, Institutional, Other, Research funding to institution: BMS; Financial Interests, Institutional, Steering Committee Member: Pfizer; Financial Interests, Institutional, Local PI: Astra-Zeneca; Financial Interests, Institutional, Funding: Aveo; Financial Interests, Institutional, Other, Study funding: Janssen. S.K. Pal: Financial Interests, Institutional, Local PI: Eisai, Genentech, Roche, Exelixis, Pfizer, CRISPR Therapeutics, Allogene Therapeutics, Xencor, Novartis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: SWOG; Other, Travel reimbursement: CRISPR, Roche. All other authors have declared no conflicts of interest.