Key clinical point: For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor tyrosine kinase inhibitor tivozanib may offer better progression-free survival and higher tolerability than sorafenib.
Major finding: Patients in the tivozanib group had significantly longer progression-free survival than sorafenib (5.6 vs. 3.9 months; P = .016).
Study details: TIVO-3 was an open-label, phase 3 trial involving 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a vascular epidermal growth factor receptor inhibitor.
Disclosures: The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.
Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.
Although tivozanib demonstrated longer progression-free survival and higher tolerability than sorafenib in the recent phase 3 TIVO-3 trial conducted by Rini and colleagues, the role of tivozanib in the treatment of metastatic renal cell carcinoma remains unclear. Critically, treatment with tivozanib in TIVO-3 was not associated with longer median overall survival than treatment with sorafenib.
In contrast, two previous phase 3 trials, METEOR and CheckMate 025, which also involved patients who had received two lines of a vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor, showed that cabozantinib or nivolumab were associated with better overall survival than standard everolimus. While the comparator was different than the TIVO-3 trial, the evidence of benefit from these previous studies is superior, based on larger population size and overall survival advantage.
Therefore, it is too early to recommend a place for tivozanib, or to say that it should be preferred over other VEGFR tyrosine kinase inhibitors.
Axel Bex, MD, PhD, is with the Royal Free London NHS Foundation Trust at the University College London. Dr. Bex reported financial relationships with Pfizer, Ipsen, Novartis, and others. His remarks are adapted from an accompanying editorial (Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30781-8).