Tivozanib Outperforms ICI Combo in Advanced RCC

The TiNivo-2 trial (NCT04987203) investigated the efficacy and safety of combining the PD-1 inhibitor nivolumab (Opdivo) with the selective VEGFR TKI tivozanib (Fotvida) in patients with advanced clear-cell renal cell carcinoma who had progressed on prior checkpoint inhibitor-based therapy.

Patients were randomized to receive tivozanib plus nivolumab or tivozanib alone. The primary endpoint was progression-free survival (PFS) as assessed by independent radiology review (IRR). The study did not meet its primary endpoint, with a median IRR-assessed PFS of 5.7 months for tivozanib–nivolumab and 7.4 months for tivozanib alone.

Subgroup analyses showed that patients who received checkpoint inhibition as their most recent prior therapy had a longer PFS with tivozanib alone compared to tivozanib–nivolumab. Overall, the results suggest that sequential checkpoint inhibitor therapy may not be beneficial for patients with advanced RCC who have progressed on prior checkpoint inhibitor-based therapy. Tivozanib monotherapy at 1.34 mg daily may be a reasonable option for second-line treatment in this setting.

Here, Toni Choueiri, MD, discusses the rationale behind this drug combination.

Transcription:

If 2α is a transcription factor at the center of all this machinery or degradation of [von Hippel–Lindau (VHL)] at the center of renal cell cancer, and if 2α govern, you know, the activity of multiple gene downstream involved in renal cell cancer carcinogenesis, proliferation, such as VEGF and others.

0:30 | So there was a lot of work on targeting it as another mechanism that could be central and more active and more beneficial, and now finally, in terms of anticancer activity. Finally, we're able to have drugs on target that are successful. [For successful], I mean, it's a toxicity-benefit ratio in favor of the responses and activity over toxicity.