As reported in The Lancet by Choueiri et al, the phase III TiNivo-2 trial has shown that immune checkpoint inhibitor rechallenge with nivolumab plus tivozanib did not improve progression-free survival vs tivozanib alone in patients with metastatic renal cell carcinoma following immune checkpoint inhibitor treatment.
Study Details
In the open-label trial, 343 patients from sites in 16 countries in Australia, Europe, North America, and South America who had disease progression during or after one to two previous lines of therapy, including one immune checkpoint inhibitor, were enrolled between November 2021 and June 2023. Patients were randomly assigned to receive nivolumab at 480 mg every 4 weeks plus tivozanib at 0.89 mg/d on the first 21 days of a 28-day cycle (n = 171) or tivozanib at 1.34 mg/d for the first 21 days of a 28-day cycle.
Treatment was continued until disease progression or unacceptable toxicity. Nivolumab could be administered for up to 2 years. The primary endpoint was progression-free survival on independent radiology review.
Key Findings
Median follow-up was 12.0 months (95% confidence interval [CI] = 11.5–12.8 months). Median progression-free survival was 5.7 months (95% CI = 4.0–7.4 months) in the nivolumab/tivozanib group vs 7.4 months (95% CI = 5.6–9.2 months) in the tivozanib group (hazard ratio [HR] = 1.10, 95% CI = 0.84–1.43, P = .49).
Among 224 patients with an immune checkpoint inhibitor as most recent previous therapy (n = 244), median progression-free survival was 7.4 months (95% CI = 5.6–9.6 months) in the nivolumab/tivozanib group vs 9.2 months (95% CI = 7.4–10.0 months) in the tivozanib group (HR = 1.10, 95% CI = 0.80–1.52, P = .56). Among 156 patients with a non–immune checkpoint inhibitor as the most recent line of therapy, median progression-free survival was 3.7 months (95% CI = 2.7–5.4 months) in the nivolumab/tivozanib group vs 3.7 months (95% CI = 1.9–7.2 months) in the tivozanib group (HR = 0.95, 95% CI = 0.61–1.50, P = .85).
Grade ≥ 3 adverse events occurred in 61% of the nivolumab/tivozanib group vs 60% of the tivozanib group. Serious adverse events occurred in 32% vs 37%. Adverse events led to treatment discontinuation in 16% vs 19%. One treatment-related death occurred in a patient in the tivozanib group (due to sepsis, renal failure, hematuria, and hypertension).
The investigators concluded: “These data further support that [immune checkpoint inhibitor] rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-[immune checkpoint inhibitor] setting.”
Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, Harvard Medical School, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Aveo Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
